REPUBLIQUE DU CAMEROUN

Paix-Travail-Patrie REPUBLIC OF CAMEROON

*********************** Peace – Work – Fatherland
UNIVERSITE DE YAOUNDE I ***********************
*********************** UNIVERSITY OF YAOUNDE I
FACULTE DES SCIENCES ***********************
*********************** FACULTY OF SCIENCE
DEPARTEMENT DE CHIMIE ***********************
INORGANIQUE DEPARTEMENT OF INORGANIC
*********************** CHEMISTRY
***********************

LABORATOIRE DE CHIMIE PHYSIQUE ET ANALYTIQUE APPLIQUÉE

LABORATORY OF ANALYTICAL AND APPLIED PHYSICAL CHEMISTRY
EQUIPE DE RECHERCHE EN CHIMIE THEORIQUE ET COMPUTATIONNELLE
THEORTICAL AND COMPUTATIONAL CHEMISTRY UNIT

Practical Work for CHEM4148

Part II: Molecular Mechanics

Title: Introduction to Molecular Docking on Chimera with AutoDock Vina and

molecular complex interactions Visualization using Biovia Discovery Studio

Counselor
Dr. Eric NJABON, MBA,
PhD Assistant
Seinior Lecturer, UY1
Academic year: Mr. Steve KAMMGUIA, MSc
Address
2023-2024 Student, UY1
nd
2 Extension, Dor 233
 TABLE OF CONTENTS

TABLE OF CONTENTS.....................................................................................................A
I- Computational Chemistry................................................................................................2
II- Purpose of the Exercise...................................................................................................2
III- Structures of ligands and proteins receptors...............................................................3
III-1- Structures of proteins receptors................................................................................3
III-2- 2D and 3D Structures of nine benzoylureas active substances...............................4
IV- Practice sample: Molecular Docking between PACRO and FLUFLIO....................6
V- Assignment........................................................................................................................6
Additional information............................................................................................................7

Dr Eric NJABON’s research team, A

University of Yaoundé I, Faculty of Science,
Laboratory of Analytical and Applied Physical Chemistry, Computational and Theoretical Chemistry Unit.
 Practical Work for CHEM4148

Introduction to Molecular Docking on Chimera with AutoDock Vina and

molecular complex interactions Visualization using Biovia Discovery Studio

I- Computational Chemistry
Computational chemistry generally refers as studies of biological systems using
technics based on molecular mechanics (MM), molecular dynamics (MD), Brownian
Dynamics (BD), Monte Carlos (MC) among others. Using MD, real life systems can be
modelled on a computer. This laboratory exercise will focus on molecular docking on the
USCF Chimera software with AutoDock Vina program between two (02) chitinase proteins of
insects (cockroach and fly) and one specific benzoylurea active substance. In order to
perform a molecular docking study, it’s important to have good ligand and a protein model
capable of being used to perform the desired studies.
A large number of protein X-ray structures can be obtained from the Protein Data Bank
(PDB). Most protein structures (enzymes) in the protein data bank have cofactor (coenzyme)
in the binding mode of the enzyme. But for this practical, we will focus in two proteins made
using homology modelling process. The Ligand for each insecticide must be provide to the
candidate. In other hand, it’s also important to know that each candidate must have three
specific software installed on his/her computer:

 UCSF Chimera;
 AutoDock Vina;
 Biovia Discovery Studio.

II- Purpose of the Exercise

The first purpose of this laboratory session is firstly to perform molecular docking
between two chitinase protein of insects and a specific benzoylurea insecticide. Secondly, it’s
aim is also to visualize, carry out and analyze different Ligand-Protein interactions in a
molecular complex. Once the different Ligand-Protein interactions are visualized and
analyses, they can give an idea of the ability of an active substance to mimic the regular
activity of a protein due to its position in the active site of the target protein. The proteins of
interest for today are cockroach Chitinase receptor from Periplaneta americana (PACRO)
and the house fly Chitinase receptor from Musca domestica (MDCRO) which are specific
enzyme involving in regulation of Chitin production into some insect cells.
In fact, Chitin is a biopolymer (linear polymer composed of N-acetyl-glucosamines) that
is widely used in nature and is produced by insects in particular. It is the major component of
the cuticle that makes up the exoskeleton in insects. The synthesis of chitin is a crucial
process for the growth and development of insect because it is the main constituent of the
cuticle that insect regularly replaces through moulting phenomena or process. Thus, the
inhibition of chitin synthesis then induces disturbances in the cuticle formation process which
Dr Eric NJABON’s research team, 2
University of Yaoundé I, Faculty of Science,
Laboratory of Analytical and Applied Physical Chemistry, Computational and Theoretical Chemistry Unit.
lead to the aborted moulting. To illustrate the impact of this disruption in insect growth, we
have the fact that without chitin, larval fleas or nymphs will never again develop a hard outer
shell (exoskeleton) and so, with their internal organs exposed to the air, insects die of
dehydration shortly after hatching or moulting (losing its old, smaller shell). This is why
inhibitors of chitin synthesis have been developed as insecticides such as benzoylureas. In
this exercise, nine types of benzoylureas will be explored.

III- Structures of ligands and proteins receptors

III-1- Structures of proteins receptors

Figure 1: 3D structure of cockoach chitinase receptor (PACRO)

Figure 2: 3D structure of house fly chitinase receptor (MDCRO)

Dr Eric NJABON’s research team, 3

University of Yaoundé I, Faculty of Science,
Laboratory of Analytical and Applied Physical Chemistry, Computational and Theoretical Chemistry Unit.
 III-2- 2D and 3D Structures of nine benzoylureas active substances

Diflu
Chlorfluazuron benzuron

Flucycloxuron

Fl Hexaflumuron
ufenoxuron

Lufenuron
Nov
aluron

Teflubenzuron T
riflumuron
Dr Eric NJABON’s research team, 4
University of Yaoundé I, Faculty of Science,
Laboratory of Analytical and Applied Physical Chemistry, Computational and Theoretical Chemistry Unit.
 Figure 3 : 2D Structures of benzylureas actives substances

Chlorflu Diflube
azuron nzuron

Flucycloxuron

Flufeno H
xuron exaflumuron

L
ufenuron
Novaluron

Teflubenzuron Triflumuron
Figure 4: 3D Structures of the nine benzoylureas active substances

Dr Eric NJABON’s research team, 5

University of Yaoundé I, Faculty of Science,
Laboratory of Analytical and Applied Physical Chemistry, Computational and Theoretical Chemistry Unit.
IV- Practice sample: Molecular Docking between PACRO and FLUFLIO
1- Perform the molecular docking (The pdb folders of optimized ligands and proteins
are in the package);
2- Complete the following table for the final score of the best complex obtained;

Complex free enthalpy

Ligand Recptor Complex Number of interactions
(kcal/mol)
PACRO Com_1 -9,2 14
FLUFLIO
MDCRO Com_2 -9 16

3- Representation of interaction on each complex

3-1- Global image of the complex
3-2- 2D and 3D representations of interactions
3-3- Complete the table of interaction presents in each complex

Complex Interaction type AA involve in interactions Distance (Å)

VAL188 2.24
Conventional hydrogen bond 2.24
GLU 146
2.62
MET 215 2.24
Carbon hydrogen bond
ASP 214 3.56
TYR213 3.24
Halogen(fluorine)
MET 215 3.34
Com_1
Pi-Anion GLU 146 4.67
Pi-sulfur MET 211 5.91
4.41
Pi-Pi stacked TRP 365
4.68
MET215 4.25
Alkyl
VAL188 3.84
Pi-Alkyl TRP105 4.69
GLU 146 3.17
Conventional hydrogen bond MET 211 3.27
VAL 188 2.30
TYR 213 3.00
Halogen(fluorine) ASP 214 3.39
MET 211 3.16
Pi-Anion GLU 146 4.87
Com_2
4.19
Pi-Pi stacked TRP 365
4.42
Pi-Pi T-staped TYR 147 5.95
Alkyl ALA 187 4.08
TYR303 4.98
Pi-Alkyl TYR 270 4.81

Dr Eric NJABON’s research team, 6

University of Yaoundé I, Faculty of Science,
Laboratory of Analytical and Applied Physical Chemistry, Computational and Theoretical Chemistry Unit.
 4.06
TRP 365
5.28
MET 211 5.15

4- Discussion (analyze and interpretate)

5- Conclude

V- Assignment
General topic: Molecular docking studies of Ligand as insecticide acting on chitinase
receptors of cockroach and house fly.
List of groups by Ligand:
Group 1: Chlorfluazuron (CHLOLIO)
Group 2: Diflubenzuron (DIFLIO)
Group 3: Flucycloxuron (FLUCLIO)
Group 4: Flufenoxuron (FLUFLIO)
Group 5: Hexaflumuron (HEXALIO)
Group 6: Lufenuron (LUFELIO)
Group 7: Novaluron (NOVALIO)
Group 8: Teflubenzuron (TEFLIO)
Group 9: Triflumuron (TRIFLIO)

1. Check your group accordingly to the list repartition of topic made during the practical
and perform molecular docking with your group’s members on your respective topic.
2. Using software like shown during the practical by the counselor, complete all the table
and instructions enumerated on part IV-.
3. Produce a short report document about your work with: a First page, a time table, a
List of abbreviation, a List of tables, a List of figures, an Introduction, a Body, a
conclusion and References.

NB: - The work is done by a group of at max three students.

- Each group will present it results and discussions in the form of a report to be
submitted within a week with the name of group members on the first page.

“Strict deadlines.”

Additional information

Dr Eric NJABON’s research team, 7

University of Yaoundé I, Faculty of Science,
Laboratory of Analytical and Applied Physical Chemistry, Computational and Theoretical Chemistry Unit.
 1. Download Chimera in your computer using the following link:
https://www.cgl.ucsf.edu/chimera/download.html and select the appropriate version
that matches your computer.
2. Download AutoDock Vina in your computer using the following link:
https://vina.scripps.edu/downloads/
3. Download Biovia Discovery Studio 21 in your computer through the following link:
https://discover.3ds.com/discovery-studio-visualizer-download

Dr Eric NJABON’s research team, 8

University of Yaoundé I, Faculty of Science,
Laboratory of Analytical and Applied Physical Chemistry, Computational and Theoretical Chemistry Unit.