International Journal of Food Science and Technology 2020, 55, 33–45 33

Review
Recent developments in molecular docking technology applied in
food science: a review

Xuan Tao,1 Yukun Huang,1,2* Chong Wang,1 Fang Chen,1 Lingling Yang,1 Li Ling,1,3 Zhenming Che1* &
Xianggui Chen1,2*
1 School of Food and Bioengineering, Xihua University, Chengdu Sichuan 610039, China
2 Key Laboratory of Food Non Thermal Processing, Engineering Technology Research Center of Food Non Thermal Processing, Yibin
Xihua University Research Institute, Yibin Sichuan 644404, China
3 College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan 611137, China

(Received 15 April 2019; Accepted in revised form 30 July 2019)

Summary Molecular docking is a theoretical simulation method based on bioinformatics, which studies the interac-
tion between molecules (such as ligands and receptors), and predicts their binding modes and affinity via
a computer platform. This technology acts as a promising mean in medicinal chemistry such as structure-
based rational drug design, which is accepted by researchers in the scientific community. During recent
years, various fundamental studies involving biomolecular interaction in the food matrix have gradually
emerged. The remarkable advantages of molecular docking such as predicting experiments are attracting
increasing attention for its application potential in various fields. This review presents the theory and soft-
ware development of molecular docking, and emphasises its application in the field of food science,
including nutritional components and food safety. Moreover, the operational mechanisms of molecular
docking are further summarised in this review.
Keywords Developments, food, interaction, mechanism, molecular docking.

docking is the most widely used one in molecular mod-

Introduction
Recognition, between two or more molecules, exists in
most life science processes (Grosdidier et al., 2011).
There has been a challenge in explaining the structural
properties and reaction mechanism of biological sys-
tems and revealing the secrets of the microcosmic
world, when studies only depend on experiments.
Molecular modelling is a general method for describ-
ing the reaction system of molecules and predicting
their macroscopic physical properties. During the last
twenty years, the development of molecular simulation
(MS) technology has exhibited significant progress,
especially since the 2013 Nobel Prize in Chemistry was
awarded (Nie et al., 2018). To date, MS technology
includes homology modelling (Nascimento et al.,
2018), molecular docking (Arthur et al., 2018) and
molecular dynamics simulation (Zhang et al., 2018),
and combines free energy calculation (Mizuguchi &
Matubayasi, 2018). Among these methods, molecular
*Correspondent: Fax: +86-28-87720552;
e-mails: hyk_diana@163.com (YH); chezhenming@163.com (ZC);
chenxianggui@hotmail.com (XC)
elling research.
In 1894, Fischer proposed the key-locking principle,
which was based on the recognition of enzyme active
sites and substrate (Sledz & Caflisch, 2018), and was
initially considered as fundamental of molecular
recognition. However, due to the limitations of the
key-locking principle, Koshland (Koshland, 2010) pro-
posed the induced-fit theory in 1958, which was
strongly supported by X-ray diffraction results. There-
fore, it is now considered as the basic principle of
molecular recognition. As early as 1982, DOCK, the
first molecular docking software appeared, encourag-
ing the development of 60 additional programs for this
purpose (Xu et al., 2016). Furthermore, molecular
docking can predict binding sites and elucidate the
mechanism of molecular recognition by simulating the
spontaneous binding process of ligands to receptors
(Brooijmans & Kuntz, 2003; Dror et al., 2013). There-
fore, it is commonly used in drug design studies (Fer-
reira et al., 2015; Forli et al., 2016; Luo et al., 2016).
Moreover, it can provide a reference for characterising
the thermodynamic and dynamic changes of inter-
molecular interactions, which not only verifies the

doi:10.1111/ijfs.14325
© 2019 Institute of Food, Science and Technology (IFSTTF)
34 Review on molecular docking in food science X. Tao et al.
experimental results at the molecular level but also
guides the actual experiment. Considering that the
food matrices are usually complex and the reactions
are diverse, molecular docking shows a great potential
in predicting the action mode and facilitating cost
reduction of experiments, which justifies extensive
application of this method in food science.
Since food provides the human body with essential
nutrients, such as proteins, lipids, carbohydrates and
vitamins, molecular docking can be widely applied in
these particular areas. Moreover, food safety issue
concerning with drug residues, biotoxins and food-
borne pathogens is one of the utmost importance in
the food research, which is increasingly involved with
molecule level study (San-Martin et al., 2015; Nakano
et al., 2018; Sledz & Caflisch, 2018). It should be
noted that the applications of molecular docking
related to food have been growing rapidly in the last
few years (as seen in Fig. 1), but barely any reviews
are available to focus on the advance of this field.
Therefore, this review aims to summarise more than
100 articles published in the recent 5 years of molecu-
lar docking applications in food science.
Molecular docking
X-ray crystal and nuclear magnetic resonance (NMR)
techniques have been used in conjunction with struc-
tural biology to analyse the structure of protein mole-
cules (Czarnota et al., 2019), even though few complex
structures between biomolecules and ligands exist.
Using the example of drug design, the method of virtual
high-throughput screening is vital in identifying the
therapeutic targets of drugs. To obtain structures that
are more complex, and to improve the efficiency of drug
Figure 1 The numbers of papers studied on ‘the applications of
molecular docking in food science’ published in Web of Science dur-
ing the last 5 years.
International Journal of Food Science and Technology 2020
design, it is particularly important to clarify the interac-
tion mechanism and binding sites between molecules.
Molecular docking can effectively predict these sites and
provides a powerful method to study them at a molecu-
lar level (Patel et al., 2016; Jaiteh et al., 2018).
Basic theory
Molecular docking is a method for predicting the posi-
tion and affinity of a ligand (small molecule) at a recep-
tor (macromolecule) binding site (Roche et al., 2015).
Scheme 1 presents the common flow chart of molecular
docking. The docking process mainly involves spatial
matching and energy matching between ligand and
receptor for optimal conformation and focuses on
agreeability. Besides, during the binding process of the
ligand to the receptor, the structure of the binding site
changes constantly until a stable bond has been success-
fully established. Only then can the charge distribution
and configuration of the binding system be determined.
The numerous interactive processes between receptors
and ligands include hydrogen bonding, electrostatic inter-
action, van der Waals forces and hydrophobic interaction.
PubChem
Convert to 3D Receptor
structure structure
Bond Length/Angle Protonation /Charge
Optimisation distribution
Conformational
formation Grid construction
Molecular
Molecular
docking
Scoring and
sorting
Complex structure
Scheme 1 The flow chart of molecular docking.
© 2019 Institute of Food, Science and Technology (IFSTTF)

In general, hydrogen bonding is produced by the covalent
bonding of hydrogen atoms with more electronegative
atoms, such as oxygen and nitrogen (Cleland, 2010). Elec-
trostatic interaction, including electrostatic gravity and
electrostatic repulsion, lacks spatial directionality (Amano
et al., 2016). The van der Waals forces either repel or
attract molecules, which are significantly weaker than
chemical bonds. Hydrophobic interaction refers to the
phenomenon of hydrophobic groups gathering close
together to avoid water (Atkins & De Paula, 2011), and
the intensity of these interacting forces is crucial in evalu-
ating the affinity between the receptors and ligands.
Types of molecular docking
The flexibility of the receptor is crucial during the pro-
cess of molecular docking and can be regulated in two
ways. One is to modify the standard rigid receptor,
while the other is to input multiple receptors, and it is
often necessary to consider the shape of the ligand, such
as ions and tautomers (Yuriev et al., 2015). Given the
above factors, molecular docking can be divided into
three types according to the degree of simplification:
rigid docking, semi-flexible docking and flexible dock-
ing.
Rigid docking
Rigid docking means that the conformation of the
docking system (receptor and ligand) does not change.
It is suitable for large systems, such as protein–protein
(Liu et al., 2016) and protein-nucleic acid (Yan &
Wang, 2013). Furthermore, rigid docking does not
require multiple calculations, making it the simplest
method.
Semi-flexible docking
During the semi-flexible docking process, the conforma-
tion of the fixed receptor remains unchanged, while the
conformation of the ligand is altered. Therefore, it is
evident that the bond length or angle of the noncritical
part of the ligand structure can be fixed (Morris et al.,
2015). Semi-flexible docking is suitable for the docking
of small molecules and macromolecules, such as pro-
teins or nucleic acids and small ligand molecules (Tiwari
& Mohanty, 2013; Jiang et al., 2016). It takes into
account the influence of changes on the ligand structure
and can be employed in a broader range of applications.
Flexible docking
During this process, the docking procedure allows the
docking system (receptor and ligand) conformation to
be readily modified. Given that the receptor and ligand
variables increase in conjunction with the number of
atoms, it is necessary to consider various additional fac-
tors. These include the fact that the calculation is sub-
stantial, and the docking process is too complicated.
© 2019 Institute of Food, Science and Technology (IFSTTF)
Review on molecular docking in food science X. Tao et al. 35
Flexible docking is generally used to study the interac-
tion between molecules accurately (Roy et al., 2018).
A comparison of molecular docking softwares
Molecular docking is achieved by using specifically
formulated software. Since the first docking program
was developed in 1982, an increasing number of
molecular docking software have emerged and are
updated constantly. However, a distinct difference in
accuracy and functionality is evident among the differ-
ent versions of docking software currently available.
More than 60 molecular docking tools have been
reported in the literature (Pagadala et al., 2017). Pre-
sently, the most commonly used docking software pri-
marily includes AutoDock (Morris et al., 2009),
DOCK (Allen et al., 2015), GOLD (Verdonk et al.,
2003), FlexX (Rarey et al., 1996), AutoDock Vina
(Trott & Olson, 2010), ICM (Schapira et al., 2003),
Glide (Friesner et al., 2004), Surflex (Jain, 2003) and
Affinity (Ring et al., 1993). As shown in Table 1
(Cross et al., 2009; Liu et al., 2018b; Salmaso &
Moro, 2018), various types of docking software are
compared in algorithms, evaluation methods, docking
accuracy, docking types, and more.
The AutoDock semi-flexible docking software consists
of two parts namely AutoGrid and AutoDock and is
mentioned in several studies. AutoGrid is used to calcu-
late the energy level contained in the lattice, while Auto-
Dock is mainly employed as a search tool to determine
optimal conformation and score. DOCK, the first molec-
ular docking software developed by Kuntz and colleagues
in 1982, is intended for rigid docking and utilises a shape-
based algorithm to determine the best site for receptor-li-
gand binding to occur. GOLD is a molecular docking
program developed by Cambridge Crystallographic Data
Centre and uses a genetic algorithm (GA) for receptor-li-
gand docking. Moreover, the docking process allows for
complete flexibility of the ligand and partial flexibility of
the receptor. The two primary applications of the FlexX
software (BioSolveIT, Sankt Augustin, Germany) include
complex prediction and virtual screening, allowing for a
protein to be docked with a group of compounds.
Although the design of the automatic docking program
AutoDock Vina is based on AutoDock, it exhibits a
higher docking accuracy and speed. Furthermore, Auto-
Dock Vina abandoned the GA and reverted to gradient
optimisation to establish the minimum point.
Molecular docking applications in food science
Protein, bioactive peptides and amino acids
Protein
Protein does not function in isolation and requires the
identification of other molecules to successfully fulfil
International Journal of Food Science and Technology 2020
36 Review on molecular docking in food science X. Tao et al.

Table 1 The comparison of molecular docking software

Accuracy
Software Algorithm Evaluation method (%) Type Speed Cost References

AutoDock Lamarckian Genetic Semi-empirical free energy 49 Semi-flexible docking Average Free Mathew et al. (2018)
algorithm (LGA)
DOCK Geometric matching The molecular force field – Semi-flexible docking Fast Free Grancieri et al. (2019)
GOLD Genetic Semi-empirical free energy 78 Flexible docking Fast Pay Kumar et al. (2017)
FlexX Incremental construction Semi-empirical free energy 58 Semi-flexible docking Fast Pay Chittepu et al. (2019)
AutoDock Broyden–Fletcher– Semi-empirical free energy 78 Semi-flexible docking Fast Free Wang et al. (2016b)
Vina Goldfarb–Shanno
ICM Stochastic global Semi-empirical free energy – Flexible docking Fast Pay Singh et al. (2014a)
optimisation
Glide Systematic search Semi-empirical free energy 82 Semi-flexible docking Average Pay Honmore et al. (2019)
Surflex Surface-based Semi-empirical free energy/the 75 Flexible docking Fast Pay Shen et al. (2018)
molecular similarity molecular force field
Affinity Monte Carlo (MC) The molecular force field – Flexible docking Slow Pay Yao et al. (2007)
LigandFit Monte Carlo (MC) The molecular force field 46 Semi-flexible docking Fast Free Ying et al. (2017)
Discovery Molecular Dynamics (MD) The molecular force field – Flexible docking Slow Free Yu et al. (2018)
Studio

its intended role (Salmaso et al., 2018). Consequently,
molecular docking methods are increasingly employed
to study the binding state of proteins and ligands and
are widely utilised in food science. The main proteins
studied in the food industry include protease and
human serum albumin (HSA).
The molecular docking technology was adopted to
study the relationship between enzyme activity and
substrates. The contact between protease and sub-
strates includes hydrogen bonding and hydrophobic
interaction, while the hydrophobic cavity of the
enzyme denotes the main binding site (Yue et al.,
2017a, 2017b). The substrate interacts with the amino
acid residues of the protease to occupy the active site
and inhibit the activity of the enzyme (Wang et al.,
2016b; Mohseni-Shahri et al., 2018). In addition, the
binding of food ingredients to enzymes triggers the
structure and conformation of the enzyme to change,
which can reduce its activity (Wang et al., 2017a).
Moreover, the study found that the binding capacity
of catechin gallate (EGCG) exceeded that of the other
three catechin isomers (epicatechin gallate (ECG), epi-
catechin (EC) and epigallocatechin (EGC)) that were
docked with trypsin. As shown in Fig. 2, s1 pocket of
trypsin was occupied by EGCG, which inhibited the
trypsin activity. The residues in the s1 pocket, namely
Ser190, Gln192, Ser195 and Val213-Ser214-Trp215,
stabilise the catechin via hydrophobic interaction and
hydrogen bonding, which provided a reference for the
design of inhibitors to control the biological activity of
trypsin (Cui et al., 2015). Moreover, some food ingre-
dients compete with enzymes to bind substrates, a

Figure 2 The structures of the catechin and

trypsin–catechin complexes. (a) The 2D
structure of EGCG. (b) The structure of the
EGCG–trypsin complex. A ball-stick model
represents EGCG, while a stick model
denotes the interaction residue. The dashed
line represents hydrophobic action (Cui
et al., 2015).

International Journal of Food Science and Technology 2020 © 2019 Institute of Food, Science and Technology (IFSTTF)

process capable of reducing enzyme activity (Zhao
et al., 2017). In food, the enzyme reaction is also pro-
moted when combined with some substances. For
example, during the binding of lignin to a-amylase, the
lignin structure is modified, and the alpha-amylase is
activated (Xie et al., 2019). These studies show that
the hydrophobic cavity of enzyme is a key binding site,
hydrogen bond and hydrophobic interaction are the
main binding force, and molecular binding enzyme
may trigger changes in enzyme structure. This is help-
ful to understand the interaction between enzyme and
substrate and the regulation of enzyme activity.
Human serum albumin is a protein found in human
plasma that transports fatty acids, amino acids, steroid
hormones, metal ions and many therapeutic molecules;
thus, it interacts with various nutrient contents taking
from food. The interaction site I and site II of HSA
between cinnamaldehyde and cinnamic acid were
established by STD-NMR experiments, which were
very coincided with the results of docking (Sun et al.,
2018). Moreover, the docking prediction was consis-
tent with the results of the thermodynamic calculation
of the binding interaction (Mu et al., 2019). The
molecular docking technology is also used to explore
the mechanisms of food dyes and HSA. The combina-
tion of quinoline yellow (QY) and HSA reduced the
free sulfhydryl group content and surface hydropho-
bicity of the protein, and provided a new understand-
ing for reducing the physiological toxicity of QY
(Wang et al., 2019b). In addition, fragrant interaction
occurred between Allura Red (AR) and Gln 196, while
the formation of hydrogen bonding took place
between AR and His 242 (Wu et al., 2015).
Bioactive peptides
Bioactive peptides (BAPS) derived from food protein
are composed of 3–20 amino acids (Manikkam et al.,
2016). Its biological activities are closely related to
human diseases and include many beneficial properties
such as antimicrobial activity, anti-inflammatory, as
well as anti-diabetic qualities (Agyei & Danquah, 2012;
Tu et al., 2018). Therefore, the preparation of novel
BAPS for oral drugs or as functional food additives to
prepare various health foods is of great significance to
human health. Based on computer simulation, bioinfor-
matics then represented a new method for discovering
BAPS (Udenigwe, 2014). Whereafter, a new tripeptide
WCW was successfully screened out from 8000 tripep-
tide libraries constructed by GOLD software, and its
IC50 value was 49 lM (Panyayai et al., 2018). Angioten-
sin-converting enzyme (ACE) inhibitory peptides are
extensively used in the treatment of hypertension. Wu
et al. (2014) employed molecular docking technology to
screen short hypotensive peptides from 113 kinds of
peptides and docked them with ACE using Discovery
Studio 3.5 software (BIOVIA, San Diego, USA). The
© 2019 Institute of Food, Science and Technology (IFSTTF)
Review on molecular docking in food science X. Tao et al. 37
use of molecular docking technology for the virtual
screening of bioactive peptides provides a directive ref-
erence and saves costs for the screening process.
Molecular docking is also widely used in identifying
BAPS (Mandal et al., 2013; Choonpicharn et al., 2016;
Ouertani et al., 2018) and evaluating their biological
activities (Xue et al., 2015; Mojica & de Mejia, 2016).
The novel ACE inhibitory peptide YLVR was purified
from wild hazelnuts, and it displayed a significantly
higher inhibitory effect due to cation–pion interaction
(Liu et al., 2018a). In addition, the peptides from
stone fish inhibited ACE activity mainly through elec-
trostatic interaction and hydrogen bonding (Auwal
et al., 2019). Two antioxidant peptides, derived from
millet protein hydrolysate, were exhibited with antioxi-
dant activity due to the interaction of threonine and
serine residues with free radicals (Agrawal et al.,
2019). According to the umami taste receptor repre-
sented by the heterodimer composed of T1R1 and
T1R3, it was discovered that T1R3 formed an open
conformation through homology modeling; whereas
T1R1 formed a closed conformation. The docking
results showed that T1R3 played a significant role dur-
ing the entire process, while T1R1 was unable to bind
with umami peptides (Dang et al., 2014). Dang (Dang
et al., 2019) proposed that monosodium glutamate
(MSG) could change the conformation of the T1R3
receptor, causing the active region to expand, which is
beneficial to the combination of umami peptides.
Amino acids
There are 20 kinds of amino acids in nature, and eight
types of essential amino acids are found in the human
body. They are the essential components of proteins
and present various positive effects. Acylation of amino
acids is one of the most common reactions. Dettori
et al. (2018) confirmed the exclusivity of L-lysine e-
amino acylation at the molecular level via flexible dock-
ing simulation and interaction energy calculation. The
study on the interaction mechanism between hydropho-
bic amino acids and b-cyclodextrin provided molecular
basis for removing the bitterness of bioactive peptides
composed of hydrophobic amino acids (Li et al., 2018).
Amino acids are capable of both activating and inhibit-
ing enzyme activity. For example, the mycosporine-like
amino acids isolated from marine sources occupied the
binding sites of proline and glycine in collagenase, thus
causing competitive inhibition (Hartmann et al., 2015).
However, the application of molecular docking in
human absorption of amino acids has yet to be sub-
jected to a comprehensive research.
Carbohydrates
Carbohydrates consist of polyhydroxy aldehydes or
polyhydroxyl ketones, as well as their condensates and
International Journal of Food Science and Technology 2020
38 Review on molecular docking in food science X. Tao et al.
derivatives. Carbohydrates in foods include glucose,
sucrose, lactose, maltose, starch and cellulose. They
play a crucial role in the physical activities of living
beings and are the primary source of energy for all liv-
ing organisms to maintain vitality.
The docking methods of polysaccharides and pro-
teins are constantly updated. A novel docking method
was proposed, which was dominated by the geometric
constraints of carbohydrate-aromatic interactions
(Yang et al., 2015). Wang et al. (2019d) studied the
effect of Ganoderma lucidum polysaccharides (GLP)
on bovine serum albumin (BSA) via molecular dock-
ing. The results showed that GLP did not interact with
the hydrophobic cavity of BSA, but with five sites on
its surface. Residues from 67 amino acids were
involved in the binding process, and the main forces
included hydrogen bonding and van der Waals forces.
The binding of carbohydrates to enzymes can modu-
late its catalytic activity. The participation of residues
of a-glucoside-H+ transporters in the transport of
AGT1 permease was studied, which provided theoreti-
cal basis for the transport mechanism of the same type
of sugar transporters (Trichez et al., 2019). Levansu-
crase catalysed the conversion of sucrose to levan, and
its residues 327 and 154 played an important role in
regulating the transfructosylation and hydrolysis activ-
ities (Xu et al., 2018). Levansucrase binding to sucrose
was beneficial to its activity in a wide range of pH
(Lee et al., 2018). In addition, simulating the binding
of sweeteners and their receptors provided an alterna-
tive direction for the design of new sweeteners (Goel
et al., 2018). Pentagalloyl-glucose (PGG) inhibited the
activity of alpha-amylase and can be used as a food
additive to maintain normal glycaemic levels (Yang
et al., 2014; Kato-Schwartz et al., 2018). Moreover,
defining the structures of receptors, ligands, binding
intermediates and complexes, as well as determining
binding sites and forces during the molecular docking
process, could provide guidance for studying the stere-
oselectivity of sugars (Bras et al., 2009).
International Journal of Food Science and Technology 2020
Lipids
Lipids are nutritionally crucial for the human body to
function efficiently, which include simple lipids, com-
pound lipids and derivative lipids in food. Pancreatic
lipase is the most important enzyme to hydrolyse diet-
ary fat and is closely related to the digestion and
absorption of fat. Its activity is affected by other sub-
stances in the environment. As shown in Fig. 3 (Du
et al., 2018), astaxanthin and p-NPB binded to pancre-
atic lipase, but there was no competition between
them. And astaxanthin acted with the adjacent resi-
dues of the catalytic site to change the conformation
of pancreatic lipase, thereby inhibiting its activity.
Eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA) are crucial lipid derivatives in human
body. Molecular docking technology has been broadly
studied in the synthesis and function of EPA and
DHA. The interaction of EPA and DHA with coen-
zyme Q10 (CoQ10) improved its permeability, which
was helpful to determine the best carrier of CoQ10
(Zulfakar et al., 2018). It was reported that amyloid-b
(Ab) can cause Alzheimer’s disease (AD) (Kotler et al.,
2014). Studies have shown that oleic acid (OA) and
DHA have direct inhibitory effects on Ab. Polyunsatu-
rated fatty acids as dietary supplements have far-
reaching significance in the treatment of AD (El Shat-
shat et al., 2019). The body can also use linoleic acid
and a-linolenic acid to synthesise EPA and DHA,
which are regulated by various enzymes. Rong et al.
(2019) docked n-3 desaturase with substrates (linolenic
acid and arachidonic acid) by using PyMOL software
(Schr€odinger, New York, USA), and then found the
molecular structure and binding domain of n-3 desat-
urase, which provided guidance for better application
of n-3 desaturase to convert n-6 polyunsaturated fatty
acid into n-3 polyunsaturated fatty acid. Ceramide
could also affect the interaction between Hsd17b4 and
Pex5 enzymes and indirectly regulate the production of
DHA (Zhu et al., 2019).
Figure 3 The docking of p-NPB and astax-
anthin to pancreatic lipase using AutoDock
4.2 (Du et al., 2018).
© 2019 Institute of Food, Science and Technology (IFSTTF)

Vitamins
Vitamins are trace organic substances that cannot be
synthesised by human body and must be obtained
from food. They play an important role in the growth,
metabolism and development of the human body (Gla-
vinic et al., 2017; Khayat et al., 2017). And some dis-
eases are inevitable with the continued lack of certain
vitamins. For example, the vitamin A deficiency is
often responsible for night blindness (Cruz et al.,
2018); the vitamin B12 deficiency can cause metabolic
disorders (Mullikin et al., 2018); and the vitamin D
deficiency can lead not only to rickets but may also be
associated with diabetes mellitus (de Oliveira & Dom-
ingueti, 2018; Abdi et al., 2019). Lin et al. (Lin et al.,
2016) studied the inhibitory effects of vitamin B2 and
D3 on xanthine oxidase (XO), between which was a
synergistic effect. The docking revealed that the main
interaction forces included hydrogen bonding,
hydrophobic interaction and van der Waals force. And
the results provided the possibility of reducing the risk
of hyperuricaemia and preventing gout through diet.
Subramanian (Subramanian et al., 2017) proposed that
the interaction sites between vitamins and their recep-
tors are Thr (314), Ile (20), Ser (16), Phe (142), Trp
(24) and Asn (315), which are more conducive to
intestinal absorption. Ascorbic acid and folic acid, two
water-soluble vitamins, inhibit the activity of human
pancreatic a-amylase (HPA). Adding vitamins to
starch reduced the rate of increase of postprandial
blood glucose level. The founding is conducive to the
development and design of new foods and drugs for
diabetics (Borah et al., 2019). Furthermore, the inter-
action between vitamin A and b-42 peptide included
hydrophobic interaction and hydrogen bonding. This
study of inhibition mechanism provided a theoretical
basis for the effective inhibition of amyloid fibrillation
and protein aggregation by vitamin A (Alam et al.,
2019). In addition, the binding of vitamins and trans-
port proteins was studied by docking technology to
determine admirable transport carriers, which provided
prerequisite for more effective absorption of vitamins
into the human body (Zulkiflee et al., 2019).
Food safety hazard factors
Pesticides and veterinary drug residues
The annual output of chemical pesticides in the world
totals nearly 2 000 000 tons. And the study focused on
the performance of pesticides and their impact on food
safety. The production and use of DDT were banned
after the 1970s due to its acute toxicity and prolonged
presence in the soil. Molecular docking was used to
initially validate the QSAR models of DDT, providing
a new method for designing high-performance pesti-
cides (Saini & Kumar, 2014). The enzymatic chemistry
© 2019 Institute of Food, Science and Technology (IFSTTF)
Review on molecular docking in food science X. Tao et al. 39
method commonly used for the rapid detection of pes-
ticides, but the sensitivity of this method is unfortu-
nately not high enough. Therefore, research
continuously aims to find a more responsive enzyme
source. Yang et al. (2016) proposed a new scoring
method, and the results of docking 219 serine hydro-
lases with 37 common organophosphorus pesticides
(Ops) illustrated that the method exhibited excellent
predictability and the sensitivity spectrum of the
enzyme was successfully obtained. Moreover, the
application of molecular docking technology can pro-
vide a basis for the establishment of biological pesti-
cide detection system. For example, four pesticides
(2,4-D, 2,4,5-T, paraquat and glyphosate) inhibited
tyrosinase activity by competing with substrates for
binding sites (Sok & Fragoso, 2018). An indirect com-
petitive enzyme-linked immunosorbent assay (icE-
LISA) was developed using succinic acid derivatives of
spinosad A as hapten, which provides a new method
for the determination of spinosad residues in fruits
and vegetables (Lan et al., 2019). Molecular docking is
also used to simulate the interaction between aptamers
and Ops (Zhang et al., 2014). Furthermore, through
molecular docking, Aamir obtained famoxadone, a
target fungicide for vascular wilt of tomato (Aamir
et al., 2018).
Veterinary drug residues have attracted significant
attention following clenbuterol poisoning. The docking
results of furan antibiotics nitrofurantoin (NFT) and
nitrofurazone (NFZ) with BSA showed that the binding
sites were located in the hydrophobic cavity of BSA,
while electrostatic and hydrophobic interactions fea-
tured prominently during the binding process (Zhang &
Ni, 2017). The directional mutagenesis of amino acid
residues was performed on the anti-sarafloxacin ScFv
antibody, and then, the affinity of the mutant antibodies
to the drug was evaluated with molecular docking
(Wang et al., 2016a). For the first time, Wang replaced
the antibody in the traditional ELISA method with the
receptor protein Rosetta-gami (DE3) and established a
tetracycline detection method, which has significant
advantages in sensitivity and detection speed (Wang
et al., 2019a). The use of aptamers in veterinary drug
detection is a new method, and the MS of selected adap-
ters to determine the mode of interaction is common.
For example, AutoDock was used in the study of flor-
fenicol aptamers (Sadeghi et al., 2018).
Biotoxins
Biotoxins are also one of the main sources of food
safety problems. Staphylococcal enterotoxin is a kind
of protein toxin produced by Staphylococcus aureus
(Argudin et al., 2010), and most food poisoning inci-
dents are caused by staphylococcal enterotoxin A
(SEA). The docking models of SEA with EC, ECG,
EGC and EGCG were compared, and the results
International Journal of Food Science and Technology 2020
40 Review on molecular docking in food science X. Tao et al.
showed that the binding ability of SEA with EGCG
was the strongest, while the common binding site was
located in the A-6 region. The spontaneous combina-
tion of EGCG and SEA occupied the active site of
SEA, thereby reducing its toxicity (Shimamura et al.,
2018). Zearalenone (ZEN) and citrinin (CIT) are con-
taminants widely existing in food and beverage. Com-
bining with HSA to form stable complexes is an
important factor to reflect their toxicological effects
(Poor et al., 2015, 2017). Classified as carcinogens by
the WHO, aflatoxins are mainly found in crops such
as soybeans, peanuts and corn, and pose a significant
danger to human health. It was reported that p-p
stacking interaction and van der Waals force are the
main factors in the interaction between antibody and
AFB1, which can be used to guide the improvement of
antibodies and their application in detection (Zhang
et al., 2019). Wang et al. (2017b) screened the binding
proteins of aflatoxin B1 (AFB1), Pim-1, trihydroxy
naphthalene reductase and gsk-3b using molecular
docking technology, and provided the 2D binding
map. In addition, Scafuro identified possible targets
for the interaction of four biotoxins with a group of
proteins (Scafuri et al., 2017). Thus, it can be seen that
molecular docking technology provides another way
for the screening of biotoxin-corresponding antibodies.
Moreover, the interaction between receptors and
ligands is expounded at the molecular level, which lays
the groundwork for rational design of efficient detec-
tion methods.
Foodborne pathogens
Foodborne pathogens can contaminate food and water
sources directly or indirectly, and cause food poison-
ing, leading to severe food safety problems. In order
to prevent food contamination, molecular docking
technology has been used to study the toxicological
effects of foodborne pathogens. Agrawal et al., (2016)
successfully screened the antimicrobial peptide Pep49,
and the specific binding of Salmonella Typhimurium
(LPS) to pep49 was validated by molecular docking.
Furthermore, the interaction between the arginine and
glutamic acid of pep49 and the abequose residue of
the O-antigen was confirmed. Listeria monocytogenes
is primarily found in refrigerated food and can grow
and reproduce at 4 °C. Therefore, it is one of the most
dangerous pathogens threatening human health, neces-
sitating focused research into various antimicrobial
agents. Reports indicated that suitable targets for new
antimicrobial binding patterns were found through the
docking of various inhibitors with the chorismate syn-
thase of L. monocytogenes (Hossain et al., 2015). In
addition, the antimicrobial agents of Vibrio cholerae
were successfully isolated and identified by molecular
docking technology combined with UV, FT-IR and
NMR (Kar et al., 2018; Rajarathinam & Dronamraju,
International Journal of Food Science and Technology 2020
2018). Furthermore, the penicillin-binding protein 4
(PBP4) might be involved in the biosynthetic pathway
of pathogen-specific peptidoglycan, further confirming
that the protein can bind well with 22 inhibitors (Sar-
angi et al., 2015). A deeper understanding of the toxi-
cological effects of foodborne pathogens, as well as the
discovery and identification of new antibacterial
agents, will help prevent and alleviate the harm caused
by foodborne pathogens.
The mechanisms of interactions between
molecules
Molecular docking is a technique for exploring the
interaction modes between molecules. The acting
forces between molecules include hydrogen bonding,
van der Waals forces, hydrophobic interaction, electro-
static interaction, p-p stacking and salt bonding (Zhu
et al., 2018; Wang et al., 2019c; Wu et al., 2019b; Yas-
rebi et al., 2019). Hydrogen bonding is produced by
the covalent bonding of hydrogen atoms with more
electronegative atoms, such as oxygen, nitrogen and
sulphur (Cleland, 2010; Liu et al., 2019; van der Lubbe
& Fonseca Guerra, 2019). The formation of hydrogen
bonding is an interatomic interaction and is generally
included in all molecular docking. The basic units of
proteins and BAPS are amino acids. Since amino acids
easily lose electrons, they are generally positively
charged. These amino acids can then interact with neg-
atively charged moieties to produce electrostatic inter-
action. Moreover, most of the BAPS and proteins
have hydrophobic cavities, allowing for effortless
hydrophobic interaction (Wu et al., 2019a). Therefore,
electrostatic interaction exists widely in the complex
containing proteins or peptides. In addition, the p-p
stacking is often formed between aromatic rings of
molecules. According to the structures of the mole-
cules, the modes of intermolecular interaction can be
predicted and verified by molecular docking. In sum-
mary, rigid docking techniques are generally used to
explore the interaction between protein molecules;
semi-flexible docking and flexible docking are usually
used to study the interaction between small molecule
compounds and other substances. After determining
the interaction force and combining with thermody-
namic experiments, the mechanism of intermolecular
interaction at the molecular level can be described
more accurately.
Conclusion, limitation and future research
In recent years, the application of molecular docking
technology in food mainly includes the screening of
receptor proteins or target molecules and the explo-
ration of intermolecular interactions, which has
brought many benefits to human. Exploring the
© 2019 Institute of Food, Science and Technology (IFSTTF)

binding mechanism of nutrients and digestive enzymes
can improve the availability of food and guide the
design of diets suitable for special populations. Simu-
lating the binding mode between harmful substances
and receptors allows for a deeper understanding of the
action mechanism. Screening and identifying safe and
nontoxic enzyme inhibitors can be used to regulate the
absorption of harmful substances and save costs. In
summary, molecular docking technology has a good
application prospect in food science.
However, it is worth noting that molecular docking
can be used to verify experimental results and provide
guidance for further research, and it does not entirely
replace the actual experiment. Many docking proce-
dures are conducted in a vacuum environment since
the real conditions such as pH, temperature and sol-
vent cannot be simulated completely. Moreover, since
the range of molecular changes during the docking
process is narrow, molecular docking is extensively
applied where proteins are involved. In addition, the
important factor to judge the accuracy of docking
results is that the receptor and ligand have known
stable structures. Therefore, the proteins in Protein
Data Bank (PDB) are often used as research objects,
the substances that cannot determine the crystal struc-
ture need to be modelled, so there are many limita-
tions.
As a result, molecular docking technology should
pay more attention to the development of algorithms
to ensure the effectiveness of docking results. It is also
necessary to design and develop docking software
based on the characteristics of the receptor and ligand.
In this way, it could promote molecular docking to
work better in the food science.
Acknowledgments
This work was partly supported by the National Natu-
ral Science Foundation of China (31801647), Sichuan
Science and Technology Program (2018JY0194,
2018SZ0340), Graduate Innovation Fund of Xihua
University (ycjj2018007), Young scholars for reserve
talent programme of Xihua University and Open
Research Fund of Key Laboratory of Traditional Chi-
nese Medicine resources in south-west China of
Chengdu University of Traditional Chinese Medicine.
Conflict of interest
The authors do not have any conflict of interest.
References
Aamir, M., Singh, V.K., Dubey, M.K. et al. (2018). In silico predic-
tion, characterization, molecular docking, and dynamic studies on
fungal SDRs as novel targets for searching potential fungicides
against fusarium wilt in tomato. Frontiers in Pharmacology, 9, 1038.
© 2019 Institute of Food, Science and Technology (IFSTTF)
Review on molecular docking in food science X. Tao et al. 41
Abdi, F., Movahedi, M., Alavi Nikje, M.M., Ghanei, L. & Mirzaie,
S. (2019). Vitamin D as a modulating agent of metformin and
insulin in patients with type 2 diabetes. Journal of Research in
Pharmacy, 23, 360–378.
Agrawal, S., Kulabhusan, P.K., Joshi, M., Bodas, D. & Paknikar,
K.M. (2016). A high affinity phage-displayed peptide as a recogni-
tion probe for the detection of Salmonella Typhimurium. Journal
of Biotechnology, 231, 40–45.
Agrawal, H., Joshi, R. & Gupta, M. (2019). Purification, identifica-
tion and characterization of two novel antioxidant peptides from
finger millet (Eleusine coracana) protein hydrolysate. Food
Research International, 120, 697–707.
Agyei, D. & Danquah, M.K. (2012). Rethinking food-derived bioac-
tive peptides for antimicrobial and immunomodulatory activities.
Trends in Food Science & Technology, 23, 62–69.
Alam, P., Siddiqi, M.K., Malik, S., Chaturvedi, S.K., Uddin, M. &
Khan, R.H. (2019). Elucidating the inhibitory potential of Vitamin
A against fibrillation and amyloid associated cytotoxicity. Interna-
tional Journal of Biological Macromolecules, 129, 333–338.
Allen, W.J., Balius, T.E., Mukherjee, S. et al. (2015). DOCK 6:
impact of new features and current docking performance. Journal
of Computational Chemistry, 36, 1132–1156.
Amano, R., Takada, K., Tanaka, Y. et al. (2016). Kinetic and ther-
modynamic analyses of interaction between a high affinity RNA
aptamer and its target protein. Biochemistry, 55, 6221–6229.
Argudin, M.A., Mendoza, M.C. & Rodicio, M.R. (2010). Food poi-
soning and staphylococcus aureus enterotoxins. Toxins, 2, 1751–
1773.
Arthur, D.E., Uzairu, A., Mamza, P., Abechi, S.E. & Shallangwa,
G.A. (2018). Structure-based optimization of tyrosine kinase inhi-
bitors: a molecular docking study. Network Modeling and Analysis
in Health Informatics and Bioinformatics, 7, 9.
Atkins, P. W. & De Paula, J. (2011). Physical Chemistry for the Life
Sciences. Pp. xxvi, 590 p. New York, Oxford: W.H. Freeman and
Co., Oxford University Press.
Auwal, S.M., Abidin, N.Z., Zarei, M., Tan, C.P. & Saari, N. (2019).
Identification, structure-activity relationship and in silico molecular
docking analyses of five novel angiotensin I-converting enzyme
(ACE)-inhibitory peptides from stone fish (Actinopyga lecanora)
hydrolysates. PLoS ONE, 14, e0197644.
Borah, P.K., Sarkar, A. & Duary, R.K. (2019). Water-soluble vita-
mins for controlling starch digestion: conformational scrambling
and inhibition mechanism of human pancreatic alpha-amylase by
ascorbic acid and folic acid. Food Chemistry, 288, 395–404.
Bras, N.F., Fernandes, P.A. & Ramos, M.J. (2009). Docking and
molecular dynamics studies on the stereoselectivity in the enzy-
matic synthesis of carbohydrates. Theoretical Chemistry Accounts,
122, 283–296.
Brooijmans, N. & Kuntz, I.D. (2003). Molecular recognition and
docking algorithms. Annual Review of Biophysics and Biomolecular
Structure, 32, 335–373.
Chittepu, V.C.S.R., Kalhotra, P., Osorio-Gallardo, T., Gallardo-
Velazquez, T. & Osorio-Revilla, G. (2019). Repurposing of FDA-
Approved NSAIDs for DPP-4 Inhibition as an Alternative for
Diabetes Mellitus Treatment: Computational and in Vitro Study.
Pharmaceutics, 11, 13.
Choonpicharn, S., Tateing, S., Jaturasitha, S., Rakariyatham, N.,
Suree, N. & Niamsup, H. (2016). Identification of bioactive peptide
from Oreochromis niloticus skin gelatin. Journal of Food Science
and Technology-Mysore, 53, 1222–1229.
Cleland, W.W. (2010). The low-barrier hydrogen bond in enzymic
catalysis. Advances in Physical Organic Chemistry, 44(44), 1–17.
Cross, J.B., Thompson, D.C., Rai, B.K. et al. (2009). Comparison of
several molecular docking programs: pose prediction and virtual
screening accuracy. Journal of Chemical Information and Modeling,
49, 1455–1474.
Cruz, S., Machado, S.N., da Cruz, S.P., Pereira, S., Saboya, C. &
Ramalho, A. (2018). Comparative study of the nutritional status of
International Journal of Food Science and Technology 2020
42 Review on molecular docking in food science X. Tao et al.
vitamin A in pregnant women and in women who became preg-
nant or did not after Roux-en-Y gastric bypass. Nutricion Hospita-
laria, 35, 421–427.
Cui, F.C., Yang, K.C. & Li, Y.Q. (2015). Investigate the binding of
catechins to trypsin using docking and molecular dynamics simula-
tion. PLoS ONE, 10, e0125848.
Czarnota, S., Johannissen, L.O., Baxter, N.J. et al. (2019). Equato-
rial active site compaction and electrostatic reorganization in cate-
chol-O-methyltransferase. Acs Catalysis, 9, 4394–4401.
Dang, Y.L., Gao, X.C., Xie, A.Y., Wu, X.Q. & Ma, F.M. (2014).
Interaction between umami peptide and taste receptor T1R1/T1R3.
Cell Biochemistry and Biophysics, 70, 1841–1848.
Dang, Y.L., Hao, L., Cao, J.X. et al. (2019). Molecular docking and
simulation of the synergistic effect between umami peptides, mono-
sodium glutamate and taste receptor T1R1/T1R3. Food Chemistry,
271, 697–706.
Dettori, L., Jelsch, C., Guiavarc’h, Y., Delaunay, S., Framboisier,
X. & Chevalot, I. (2018). Molecular rules for selectivity in lipase-
catalysed acylation of lysine. Process Biochemistry, 74, 50–60.
Dror, R.O., Green, H.F., Valant, C. et al. (2013). Structural basis
for modulation of a G-protein-coupled receptor by allosteric drugs.
Nature, 503, 295-+.
Du, X.P., Bai, M.L., Huang, Y. et al. (2018). Inhibitory effect of
astaxanthin on pancreatic lipase with inhibition kinetics integrating
molecular docking simulation. Journal of Functional Foods, 48,
551–557.
El Shatshat, A., Pham, A.T. & Rao, P.P.N. (2019). Interactions of
polyunsaturated fatty acids with amyloid peptides A beta 40 and A
beta 42. Archives of Biochemistry and Biophysics, 663, 34–43.
Ferreira, L.G., dos Santos, R.N., Oliva, G. & Andricopulo, A.D.
(2015). Molecular docking and structure-based drug design strate-
gies. Molecules, 20, 13384–13421.
Forli, S., Huey, R., Pique, M.E., Sanner, M.F., Goodsell, D.S. &
Olson, A.J. (2016). Computational protein-ligand docking and vir-
tual drug screening with the AutoDock suite. Nature Protocols, 11,
905–919.
Friesner, R.A., Banks, J.L., Murphy, R.B. et al. (2004). Glide: a
new approach for rapid, accurate docking and scoring. 1. Method
and assessment of docking accuracy. Journal of Medicinal Chem-
istry, 47, 1739–1749.
Glavinic, U., Stankovic, B., Draskovic, V. et al. (2017). Dietary
amino acid and vitamin complex protects honey bee from immuno-
suppression caused by Nosema ceranae. PLoS ONE, 12, e0187726.
Goel, A., Gajula, K., Gupta, R. & Rai, B. (2018). In-silico predic-
tion of sweetness using structure-activity relationship models. Food
Chemistry, 253, 127–131.
Grancieri, M., Martino, H.S.D. & De Mejia, E.G. (2019).
Digested total protein and protein fractions from chia seed (Sal-
via hispanica L.) had high scavenging capacity and inhibited
5-LOX, COX-1-2, and iNOS enzymes. Food Chemistry, 289,
204–214.
Grosdidier, A., Zoete, V. & Michielin, O. (2011). SwissDock, a pro-
tein-small molecule docking web service based on EADock DSS.
Nucleic Acids Research, 39, W270–W277.
Hartmann, A., Gostner, J., Fuchs, J.E. et al. (2015). Inhibition of
collagenase by mycosporine-like amino acids from marine sources.
Planta Medica, 81, 813–820.
Hossain, M.M., Roy, P.K., Mosnaz, A.T.M.J., Shakil, S.K., Hasan,
M.M. & Prodhan, S.H. (2015). Structural analysis and molecular
docking of potential ligands with chorismate synthase of Listeria
monocytogenes: a novel antibacterial drug target. Indian Journal of
Biochemistry & Biophysics, 52, 45–59.
Honmore, V.S., Kandhare, A.D., Kadam, P.P., Khedkar, V.M.,
Natu, A.D. & Rojatkar, S.R. (2019). Diarylheptanoid, a con-
stituent isolated from methanol extract of Alpinia officinarum
attenuates TNF-alpha level in Freund’s complete adjuvant-induced
arthritis in rats. Journal of Ethnopharmacology, 229, 233–245.
International Journal of Food Science and Technology 2020
Jain, A.N. (2003). Surflex: fully automatic flexible molecular docking
using a molecular similarity-based search engine. Journal of Medic-
inal Chemistry, 46, 499–511.
Jaiteh, M., Zeifman, A., Saarinen, M. et al. (2018). Docking screens
for dual inhibitors of disparate drug targets for Parkinson’s dis-
ease. Journal of Medicinal Chemistry, 61, 5269–5278.
Jiang, W., Li, W.J., Hong, Y., Wang, S.Z. & Fang, B.S. (2016).
Cloning, expression, mutagenesis library construction of glycerol
dehydratase, and binding mode simulation of its reactivase with
ligands. Applied Biochemistry and Biotechnology, 178, 739–752.
Kar, S., Mishra, R.K., Pathak, A., Dikshit, A. & Rao, G.N. (2018).
In silico modeling and synthesis of phenyl and thienyl analogs of
chalcones for potential leads as anti-bacterial agents. Journal of
Molecular Structure, 1156, 433–440.
Kato-Schwartz, C.G., Bracht, F., Goncalves, G.D. et al. (2018).
Inhibition of alpha-amylases by pentagalloyl glucose: kinetics,
molecular dynamics and consequences for starch absorption. Jour-
nal of Functional Foods, 44, 265–273.
Khayat, S., Fanaei, H. & Ghanbarzehi, A. (2017). Minerals in preg-
nancy and lactation: a review article. Journal of Clinical and Diag-
nostic Research, 11, Qe1-Qe5.
Koshland, D.E. (2010). The key–lock theory and the induced fit the-
ory. Angewandte Chemie International Edition, 33, 2375–2378.
Kotler, S.A., Walsh, P., Brender, J.R. & Ramamoorthy, A. (2014).
Differences between amyloid-beta aggregation in solution and on
the membrane: insights into elucidation of the mechanistic details
of Alzheimer’s disease. Chemical Society Reviews, 43, 6692–6700.
Kumar, P.N., Swapna, T.H., Khan, M.Y., Daddam, J.R. &
Hameeda, B. (2017). Molecular dynamics and protein interaction
studies of lipopeptide (Iturin A) on alpha- amylase of Spodoptera
litura. Journal of Theoretical Biology, 415, 41–47.
Lan, J.Q., Zhao, H.W., Jin, X.T. et al. (2019). Development of a
monoclonal antibody-based immunoaffinity chromatography and a
sensitive immunoassay for detection of spinosyn A in milk, fruits,
and vegetables. Food Control, 95, 196–205.
Lee, S.Y., Shin, W.R., Sekhon, S.S. et al. (2018). Molecular docking
analysis and biochemical evaluation of levansucrase from sphingo-
bium chungbukense DJ77. Acs Combinatorial Science, 20, 414–422.
Li, J.Q., Geng, S., Liu, B.G., Wang, H.B. & Liang, G.Z. (2018).
Self-assembled mechanism of hydrophobic amino acids and beta-
cyclodextrin based on experimental and computational methods.
Food Research International, 112, 136–142.
Lin, S.Y., Zhang, G.W., Liao, Y.J. & Gong, D.M. (2016). The inhi-
bitory kinetics and mechanism of dietary vitamins D-3 and B-2 on
xanthine oxidase. Food & Function, 7, 2849–2861.
Liu, W.P., Liu, G.J., Zhou, H.Y., Fang, X., Fang, Y. & Wu, J.H.
(2016). Computer prediction of paratope on antithrombotic anti-
body 10B12 and epitope on platelet glycoprotein VI via molecular
dynamics simulation. Biomedical Engineering Online, 15.
Liu, C.L., Fang, L., Min, W.H., Liu, J.S. & Li, H.M. (2018a). Explo-
ration of the molecular interactions between angiotensin-I-converting
enzyme (ACE) and the inhibitory peptides derived from hazelnut
(Corylus heterophylla Fisch.). Food Chemistry, 245, 471–480.
Liu, Z., Liu, Y., Zeng, G. et al. (2018b). Application of molecular
docking for the degradation of organic pollutants in the environ-
mental remediation: a review. Chemosphere, 203, 139–150.
Liu, Z.Y., Hu, J.W., Huang, C.H. et al. (2019). Sulfur-based
intramolecular hydrogen-bond: excited-state hydrogen-bond on/off
switch with dual room-temperature phosphorescence. Journal of
the American Chemical Society, 141, 9885–9894.
van der Lubbe, S.C.C. & Fonseca Guerra, C. (2019). The nature of
hydrogen bonds: a delineation of the role of different energy com-
ponents on hydrogen bond strengths and lengths. Chemistry–An
Asian Journal, 14(16), 2760–2769.
Luo, H., Mattes, W., Mendrick, D.L. & Hong, H.X. (2016). Molecu-
lar docking for identification of potential targets for drug repur-
posing. Current Topics in Medicinal Chemistry, 16, 3636–3645.
© 2019 Institute of Food, Science and Technology (IFSTTF)

Mandal, S.M., Porto, W.F., Dey, P., Maiti, M.K., Ghosh, A.K. &
Franco, O.L. (2013). The attack of the phytopathogens and the
trumpet solo: identification of a novel plant antifungal peptide with
distinct fold and disulfide bond pattern. Biochimie, 95, 1939–1948.
Manikkam, V., Vasiljevic, T., Donkor, O.N. & Mathai, M.L. (2016).
A review of potential marine-derived hypotensive and anti-obesity
peptides. Critical Reviews in Food Science and Nutrition, 56, 92–
112.
Mathew, B., Baek, S.C., Parambi, D.G.T., Lee, J.P., Joy, M. &
Rilda, P.R.A. (2018). Selected aryl thiosemicarbazones as a new
class of multi-targeted monoamine oxidase inhibitors. Medchem-
comm, 9, 1871–1881.
Mizuguchi, T. & Matubayasi, N. (2018). Free-energy analysis of pep-
tide binding in lipid membrane using all-atom molecular dynamics
simulation combined with theory of solutions. Journal of Physical
Chemistry B, 122, 3219–3229.
Mohseni-Shahri, F.S., Moeinpour, F. & Nosrati, M. (2018). Spec-
troscopy and molecular dynamics simulation study on the interac-
tion of sunset yellow food additive with pepsin. International
Journal of Biological Macromolecules, 115, 273–280.
Mojica, L. & de Mejia, E.G. (2016). Optimization of enzymatic pro-
duction of anti-diabetic peptides from black bean (Phaseolus vul-
garis L.) proteins, their characterization and biological potential.
Food & Function, 7, 713–727.
Morris, G.M., Huey, R., Lindstrom, W. et al. (2009). AutoDock4
and AutoDockTools4: automated docking with selective receptor
flexibility. Journal of Computational Chemistry, 30, 2785–2791.
Morris, G.M., Goodsell, D.S., Halliday, R.S. et al. (2015). Auto-
mated docking using a Lamarckian genetic algorithm and an
empirical binding free energy function. Journal of Computational
Chemistry, 19, 1639–1662.
Mu, H.T., Chen, S.H., Liu, F.Y. et al. (2019). Stereoselective inter-
actions of lactic acid enantiomers with HSA: spectroscopy and
docking application. Food Chemistry, 270, 429–435.
Mullikin, D., Pillai, N., Sanchez, R. et al. (2018). Megaloblastic ane-
mia progressing to severe thrombotic microangiopathy in patients
with disordered vitamin B-12 metabolism: case reports and litera-
ture review. Journal of Pediatrics, 202, 315-+.
Nakano, S., Megro, S.I., Hase, T. et al. (2018). Computational
molecular docking and x-ray crystallographic studies of catechins
in new drug design strategies. Molecules, 23, pii: E2020.
Nascimento, K.S., Araripe, D.A., Pinto, V.R. et al. (2018). Homol-
ogy modeling, molecular docking, and dynamics of two alpha-
methyl-D-mannoside-specific lectins from Arachis genus. Journal of
Molecular Modeling, 24, 251.
Nie, X.H., Zhao, L., Deng, S., Su, W. & Zhang, Y. (2018). A review
of molecular simulation applied in vapor-liquid equilibria (VLE)
estimation of thermodynamic cycles. Journal of Molecular Liquids,
264, 652–674.
de Oliveira, V.R.L.S. & Domingueti, C.P. (2018). Association of
vitamin D deficiency and type 1 diabetes mellitus: a systematic
review and meta-analysis. International Journal of Diabetes in
Developing Countries, 38, 280–288.
Ouertani, A., Chaabouni, I., Mosbah, A. et al. (2018). Two new
secreted proteases generate a casein-derived antimicrobial peptide
in bacillus cereus food born isolate leading to bacterial competition
in milk. Frontiers in Microbiology, 9, 1148.
Pagadala, N.S., Syed, K. & Tuszynski, J. (2017). Software for molec-
ular docking: a review. Biophys Rev, 9, 91–102.
Panyayai, T., Sangsawad, P., Pacharawongsakda, E., Sawat-
dichaikul, O., Tongsima, S. & Choowongkomon, K. (2018). The
potential peptides against angiotensin-I converting enzyme through
a virtual tripeptide-constructing library. Computational Biology and
Chemistry, 77, 207–213.
Patel, S., Patel, B. & Bhatt, H. (2016). 3D-QSAR studies on 5-hy-
droxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide derivatives as
HIV-1 integrase inhibitors. Journal of the Taiwan Institute of
Chemical Engineers, 59, 61–68.
© 2019 Institute of Food, Science and Technology (IFSTTF)
Review on molecular docking in food science X. Tao et al. 43
Poor, M., Lemli, B., Balint, M. et al. (2015). Interaction of Citrinin
with Human Serum Albumin. Toxins, 7, 5155–5166.
Poor, M., Kunsagi-Mate, S., Balint, M., Hetenyi, C., Gerner, Z. &
Lemli, B. (2017). Interaction of mycotoxin zearalenone with human
serum albumin. Journal of Photochemistry and Photobiology B-Biol-
ogy, 170, 16–24.
Rajarathinam, G. & Dronamraju, S.V.L. (2018). In vitro and in silico
antimicrobial activity of sterol and flavonoid isolated from Tri-
anthema decandra L. Microbial Pathogenesis, 121, 77–86.
Rarey, M., Kramer, B., Lengauer, T. & Klebe, G. (1996). A fast
flexible docking method using an incremental construction algo-
rithm. Journal of Molecular Biology, 261, 470–489.
Ring, C.S., Sun, E., McKerrow, J.H. et al. (1993). Structure-based
inhibitor design by using protein models for the development of
antiparasitic agents. Proceedings of the National Academy of
Sciences of the United States of America, 90, 3583–3587.
Roche, D.B., Brackenridge, D.A. & McGuffin, L.J. (2015). Proteins
and their interacting partners: an introduction to protein-ligand
binding site prediction methods. International Journal of Molecular
Sciences, 16, 29829–29842.
Rong, C.C., Chen, H.Q., Tang, X. et al. (2019). Characterization
and molecular docking of new 17 fatty acid desaturase genes from
Rhizophagus irregularis and Octopus bimaculoides. Rsc Advances,
9, 6871–6880.
Roy, S., Narang, B.K., Gupta, M.K., Abbot, V., Singh, V. &
Rawal, R.K. (2018). Molecular docking studies on isocytosine
analogues as xanthine oxidase inhibitors. Drug Research, 68, 395–
402.
Sadeghi, A.S., Mohsenzadeh, M., Abnous, K., Taghdisi, S.M. &
Ramezani, M. (2018). Development and characterization of DNA
aptamers against florfenicol: fabrication of a sensitive fluorescent
aptasensor for specific detection of florfenicol in milk. Talanta,
182, 193–201.
Saini, V. & Kumar, A. (2014). QSAR analyses of DDT analogues
and their in silico validation using molecular docking study against
voltage-gated sodium channel of Anopheles funestus. Sar and Qsar
in Environmental Research, 25, 777–790.
Salmaso, V. & Moro, S. (2018). Bridging molecular docking to
molecular dynamics in exploring ligand-protein recognition pro-
cess: an overview. Frontiers in Pharmacology, 9, 923.
Salmaso, V., Sturlese, M., Cuzzolin, A. & Moro, S. (2018). Combin-
ing self- and cross-docking as benchmark tools: the performance of
DockBench in the D3R Grand Challenge 2. Journal of Computer-
Aided Molecular Design, 32, 251–264.
San-Martin, A., Donoso, V., Leiva, S. et al. (2015). Molecular dock-
ing studies of the antitumoral activity and characterization of new
chalcone. Current Topics in Medicinal Chemistry, 15, 1743–1749.
Sarangi, A.N., Lohani, M. & Aggarwal, R. (2015). Proteome mining
for drug target identification in Listeria monocytogenes strain
EGD-e and structure-based virtual screening of a candidate drug
target penicillin binding protein 4. Journal of Microbiological Meth-
ods, 111, 9–18.
Scafuri, B., Varriale, A., Facchiano, A., D’Auria, S., Raggi, M.E. &
Marabotti, A. (2017). Binding of mycotoxins to proteins involved
in neuronal plasticity: a combined in silico/wet investigation. Scien-
tific Reports, 7, 15156.
Schapira, M., Abagyan, R. & Totrov, M. (2003). Nuclear hormone
receptor targeted virtual screening. Journal of Medicinal Chemistry,
46, 3045–3059.
Shen, C., Wang, Z., Yao, X., Li, Y., Lei, T. & Wang, E. (2018).
Comprehensive assessment of nine docking programs on type II
kinase inhibitors: prediction accuracy of sampling power, scoring
power and screening power. Briefings in Bioinformatics, https://doi.
org/10.1093/bib/bby103
Shimamura, Y., Utsumi, M., Hirai, C. et al. (2018). Binding of cate-
chins to staphylococcal enterotoxin A. Molecules, 23, pii: E1125.
Singh, D., Sharma, K.K., Jacob, S. & Gakhar, S.K. (2014a). Molec-
ular docking of laccase protein from bacillus safensis DSKK5
International Journal of Food Science and Technology 2020
44 Review on molecular docking in food science X. Tao et al.
Isolated from earthworm gut: A novel method to study dye Decol-
orization Potential. Water Air & Soil Pollution, 225, 2175.
Sledz, P. & Caflisch, A. (2018). Protein structure-based drug design:
from docking to molecular dynamics. Current Opinion in Structural
Biology, 48, 93–102.
Sok, V. & Fragoso, A. (2018). Kinetic, spectroscopic and computa-
tional docking study of the inhibitory effect of the pesticides 2,4,5-
T, 2,4-D and glyphosate on the diphenolase activity of mushroom
tyrosinase. International Journal of Biological Macromolecules, 118,
427–434.
Subramanian, V.S., Sabui, S., Teafatiller, T., Bohl, J.A. & Said,
H.M. (2017). Structure/functional aspects of the human riboflavin
transporter-3 (SLC52A3): role of the predicted glycosylation and
substrate-interacting sites. American Journal of Physiology-Cell
Physiology, 313, C228–C238.
Sun, Q.M., Yang, H.Q., Tang, P.X., Liu, J.Y., Wang, W. & Li, H.
(2018). Interactions of cinnamaldehyde and its metabolite cinnamic
acid with human serum albumin and interference of other food
additives. Food Chemistry, 243, 74–81.
Tiwari, G. & Mohanty, D. (2013). An in silico analysis of the bind-
ing modes and binding affinities of small molecule modulators of
PDZ-peptide interactions. PLoS ONE, 8, e71340.
Trichez, D., Knychala, M.M., Figueiredo, C.M. et al. (2019). Key
amino acid residues of the AGT1 permease required for mal-
totriose consumption and fermentation by Saccharomyces cere-
visiae. Journal of Applied Microbiology, 126, 580–594.
Trott, O. & Olson, A.J. (2010). Software news and update Auto-
Dock Vina: improving the speed and accuracy of docking with a
new scoring function, efficient optimization, and multithreading.
Journal of Computational Chemistry, 31, 455–461.
Tu, M.L., Cheng, S.Z., Lu, W.H. & Du, M. (2018). Advancement
and prospects of bioinformatics analysis for studying bioactive
peptides from food-derived protein: Sequence, structure, and func-
tions. Trac-Trends in Analytical Chemistry, 105, 7–17.
Udenigwe, C.C. (2014). Bioinformatics approaches, prospects and
challenges of food bioactive peptide research. Trends in Food
Science & Technology, 36, 137–143.
Verdonk, M.L., Cole, J.C., Hartshorn, M.J., Murray, C.W. & Tay-
lor, R.D. (2003). Improved protein-ligand docking using GOLD.
Proteins-Structure Function and Genetics, 52, 609–623.
Wang, J.P., Dong, J., Duan, C.F. et al. (2016a). Production and
directional evolution of antisarafloxacin ScFv antibody for
immunoassay of fluoroquinolones in milk. Journal of Agricultural
and Food Chemistry, 64, 7957–7965.
Wang, Y.Q., Zhang, H.M., Kang, Y.J., Gu, Y.L. & Cao, J. (2016b).
Mechanism of curcumin-induced trypsin inhibition: computational
and experimental studies. Journal of Molecular Structure, 1107, 91–
98.
Wang, J., Chan, C., Huang, F.W. et al. (2017a). Interaction mecha-
nism of pepsin with a natural inhibitor gastrodin studied by spec-
troscopic methods and molecular docking. Medicinal Chemistry
Research, 26, 405–413.
Wang, Y., Liu, J.F., Zhang, L.J., He, X. & Zhang, J.Z.H. (2017b).
Computational search for aflatoxin binding proteins. Chemical
Physics Letters, 685, 1–8.
Wang, G., Zhang, H.C., Liu, J. & Wang, J.P. (2019a). A receptor-
based chemiluminescence enzyme linked immunosorbent assay for
determination of tetracyclines in milk. Analytical Biochemistry,
564, 40–46.
Wang, R., Hu, X., Pan, J.H., Gong, D.M. & Zhang, G.W. (2019b).
Interaction between quinoline yellow and human serum albumin:
spectroscopic, chemometric and molecular docking studies. Journal
of the Science of Food and Agriculture, 99, 73–82.
Wang, W.J., Gan, N., Sun, Q.M. et al. (2019c). Study on the inter-
action of ertugliflozin with human serum albumin in vitro by multi-
spectroscopic methods, molecular docking, and molecular
dynamics simulation. Spectrochimica Acta Part a-Molecular and
Biomolecular Spectroscopy, 219, 83–90.
International Journal of Food Science and Technology 2020
Wang, Y.Q., Wang, Y., Luo, Q., Zhang, H.M. & Cao, J. (2019d).
Molecular characterization of the effects of Ganoderma Lucidum
polysaccharides on the structure and activity of bovine serum albu-
min. Spectrochimica Acta Part a-Molecular and Biomolecular Spec-
troscopy, 206, 538–546.
Wu, H.X., Liu, Y.L., Guo, M.R., Xie, J.L. & Jiang, X.M. (2014). A
virtual screening method for inhibitory peptides of angiotensin i-
converting enzyme. Journal of Food Science, 79, C1635–C1642.
Wu, D., Yan, J., Wang, J., Wang, Q. & Li, H. (2015). Characterisa-
tion of interaction between food colourant allura red AC and
human serum albumin: multispectroscopic analyses and docking
simulations. Food Chemistry, 170, 423–429.
Wu, C., Ma, W.C. & Hua, Y.F. (2019a). The relationship between
breaking force and hydrophobic interactions or disulfide bonds
involved in heat-induced soy protein gels as affected by heating
time and temperature. International Journal of Food Science and
Technology, 54, 231–239.
Wu, D., Duan, R., Geng, F., Hu, X., Gan, N. & Li, H. (2019b).
Comparative analysis of the interaction of mono-, dis-, and tris-
azo food dyes with egg white lysozyme: a combined spectroscopic
and computational simulation approach. Food Chemistry, 284,
180–187.
Xie, F., Zhang, W., Gong, S.X. et al. (2019). Investigating lignin
from Canna edulis ker residues induced activation of alpha-amy-
lase: kinetics, interaction, and molecular docking. Food Chemistry,
271, 62–69.
Xu, M., Caflisch, A. & Hamm, P. (2016). Protein structural memory
influences ligand binding mode(s) and unbinding rates. Journal of
Chemical Theory and Computation, 12, 1393–1399.
Xu, W., Ni, D.W., Yu, S.H., Zhang, T. & Mu, W.M. (2018).
Insights into hydrolysis versus transfructosylation: mutagenesis
studies of a novel levansucrase from Brenneria sp EniD312. Inter-
national Journal of Biological Macromolecules, 116, 335–345.
Xue, Z.H., Wen, H.C., Zhai, L.J. et al. (2015). Antioxidant activity
and anti-proliferative effect of a bioactive peptide from chickpea
(Cicer arietinum L.). Food Research International, 77, 75–81.
Yan, Z.Q. & Wang, J. (2013). Optimizing scoring function of pro-
tein-nucleic acid interactions with both affinity and specificity.
PLoS ONE, 8, e74443.
Yang, J.P., He, H. & Lu, Y.H. (2014). Four flavonoid compounds
from phyllostachys edulis leaf extract retard the digestion of starch
and its working mechanisms. Journal of Agricultural and Food
Chemistry, 62, 7760–7770.
Yang, Y., Qian, J. & Ming, D. (2015). Docking polysaccharide to
proteins that have a Tryptophan box in the binding pocket. Carbo-
hydrate Research, 414, 78–84.
Yang, L.L., Yang, X., Li, G.B., Fan, K.G., Yin, P.F. & Chen, X.G.
(2016). An integrated molecular docking and rescoring method for
predicting the sensitivity spectrum of various serine hydrolases to
organophosphorus pesticides. Journal of the Science of Food and
Agriculture, 96, 2184–2192.
Yao, Y.A., Han, W.W., Zhou, Y.H., Li, Z.S., Li, Q. & Zhong, D.F.
(2007). Molecular docking study of the affinity of CYP2C9 and
CYP2D6 for imrecoxib. Journal of Theoretical & Computational
Chemistry, 6, 541–548.
Yasrebi, S.A., Takjoo, R. & Riazi, G.H. (2019). HSA-interaction
studies of uranyl complexes of alkyl substituted isothiosemicar-
bazone. Journal of Molecular Structure, 1193, 53–61.
Ying, H.Z., Xie, J.F., Liu, X.G., Yao, T.T., Dong, X.W. & Hu,
C.Q. (2017). Discriminatory analysis based molecular docking
study for in silico identification of epigallocatechin-3-gallate
(EGCG) derivatives as B-Raf(V600E) inhibitors. Rsc Advances, 7,
44820–44826.
Yue, Y.Y., Zhao, S.F., Liu, J.M., Yan, X.Y. & Sun, Y.Y. (2017a).
Probing the binding properties of dicyandiamide with pepsin by
spectroscopy and docking methods. Chemosphere, 185, 1056–1062.
Yue, Y.Y., Zhao, S.F., Sun, Y.Y., Yan, X.Y., Liu, J.M. & Zhang, J.
(2017b). Effects of plant extract aurantio-obtusin on pepsin
© 2019 Institute of Food, Science and Technology (IFSTTF)

structure: spectroscopic characterization and docking simulation.
Journal of Luminescence, 187, 333–339.
Yu, Z.P., Wu, S.J., Zhao, W.Z., Ding, L., Fan, Y. & Shiuan, D.
(2018). Anti-Alzheimers activity and molecular mechanism of albu-
min-derived peptides against AChE and BChE. Food & Function,
9, 1173–1178.
Yuriev, E., Holien, J. & Ramsland, P.A. (2015). Improvements,
trends, and new ideas in molecular docking: 2012-2013 in review.
Journal of Molecular Recognition, 28, 581–604.
Zhang, Q.L. & Ni, Y.N. (2017). Comparative studies on the interac-
tion of nitrofuran antibiotics with bovine serum albumin. Rsc
Advances, 7, 39833–39841.
Zhang, C.Z., Wang, L., Tu, Z. et al. (2014). Organophosphorus pes-
ticides detection using broad-specific single-stranded DNA based
fluorescence polarization aptamer assay. Biosensors & Bioelectron-
ics, 55, 216–219.
Zhang, N., Huo, J., Yang, B.Y. et al. (2018). Understanding of imida-
zolium group hydration and polymer structure for hydroxide anion
conduction in hydrated imidazolium-g-PPO membrane by molecular
dynamics simulations. Chemical Engineering Science, 192, 1167–1176.
Zhang, F.Y., Liu, B., Zhang, Y. et al. (2019). Application of CdTe/
CdS/ZnS quantum dot in immunoassay for aflatoxin B1 and
© 2019 Institute of Food, Science and Technology (IFSTTF)
Review on molecular docking in food science X. Tao et al. 45
molecular modeling of antibody recognition. Analytica Chimica
Acta, 1047, 139–149.
Zhao, L.D., Guo, R.H., Sun, Q.M., Lan, J.W. & Li, H. (2017).
Interaction between azo dye Acid Red 14 and pepsin by multispec-
tral methods and docking studies. Luminescence, 32, 1123–1130.
Zhu, W., Jia, Y.Y., Peng, J.M. & Li, C.M. (2018). Inhibitory effect
of persimmon tannin on pancreatic lipase and the underlying
mechanism in vitro. Journal of Agricultural and Food Chemistry, 66,
6013–6021.
Zhu, Z., Chen, J., Wang, G. et al. (2019). Ceramide regulates inter-
action of Hsd17b4 with Pex5 and function of peroxisomes.
Biochimica et biophysica acta. Molecular and Cell Biology of
Lipids, 1864(10), 1514–1524.
Zulfakar, M.H., Chan, L.M., Rehman, K., Wai, L.K. & Heard,
C.M. (2018). Coenzyme Q10-loaded fish oil-based Bigel system:
probing the delivery across porcine skin and possible interaction
with fish oil fatty acids. An Official Journal of the American Associ-
ation of Pharmaceutical Scientists, 19, 1116–1123.
Zulkiflee, N.S., Awang, S.A., Woo, X.M., Kamilan, M.F.W.I.,
Mariappan, M.Y. & Tan, J.-K. (2019). In silico docking of vitamin
E isomers on transport proteins. Current Computer-Aided Drug
Design, https://doi.org/123.10.2174/1573409915666190614113733
International Journal of Food Science and Technology 2020