#034 Rational Nanocarrier Design Principles For Lipid-Like Compounds

1
Sabanci University
ENS 491-492 Project Final Report
#034 Rational Nanocarrier Design Principles for Lipid-like

Compounds
mer Acar
Supervised by
Canan Atlgan
In
Faculty of Engineering and Natural Sciences
Istanbul, Fall 2016
Contents
1.
2.
3.
4.
5.
6.
Introduction
Methodology
Results
Conclusion and Future work
References
Appendix
3
4
10
19
20
21
1. Introduction
Small interference RNA (siRNA) is one of the most studied types of RNAi. siRNA has the ability
to bind to a specific mRNA which provides silencing of specific genes and due to inhibition of
the related protein synthesis and decrease the related protein level. siRNA can be also
designed with respect to the target gene sequence. Clinical trials are being developed to show
the efficacy and safety of siRNA as a treatment of cancer1. However, there are several
challenges for in vivo delivery of siRNA to cells. Off-target effect, sensitivity of siRNA molecules
to enzymatic degradation, rapid renal clearance, provocation of immune system, and inability
to pass through cell membrane are the reasons causing the challenges2. Using nanocarriers
for siRNA delivery is one of the possible and effective solutions for these problems.
Nanocarriers have several advantages which can be listed as3 :
1. Protection of siRNA molecule from enzymatic degradation and response of immune
system
2. More efficient transportation of siRNA molecules through cell membrane
3. Nanocarriers can be modified for targeted delivery
4. Ability to carry different therapeutic agents with siRNA
There are several different types of nanocarriers such as lipid based, polymer based and
inorganic nanoparticles. Lipidoids are lipid based nanoparticles which have differences from
typical cationic lipids in terms of number of tail groups attached to amine core and also less
distinction between head and tail elements. Because they have lipid-like features and selfassembly behaviors, lipidoids are promising in terms of in vivo delivery of siRNA and also codelivery of siRNA with other anti-cancer agents.
Figure 1. siRNA transportation with lipidoid molecules3
This report summarizes what has been done and current status of the project. C14-113 lipidoid
structure is synthesized by Love et al 4. C14 represents that the hydrophobic chains of lipidoid
has 14 carbon atoms and 113 is an arbitrary number for certain type of amine. This structure
is chosen because it has higher efficiency of silencing over other structures in the lipidoid
library of Love et al. Clustering dynamics of several different systems with this lipidoid were
analyzed with atomistic Molecular Dynamics (MD) and Dissipative particle Dynamics (DPD)
simulations. In the first half of the project I performed MD simulations in order to observe the
behavior that can be seen in fig 1. After performing several simulations in atomistic manner,
in order to overcome the time barrier of the atomistic simulations, I applied DPD methods for
the second half of the project. It was not possible to model the system within DPD framework
because of electrostatic interactions that inhibits the minimization process of the system. For
the last part of the project I tried to mimic the behavior of the system by scanning parameter
space for DPD simulations so that I can find related parameters to form a capsid.
2. Methodology
2.1.
Atomistic Molecular Dynamics
2.1.1. Initial Structure Design
Initial structure of lipidoid molecules was drawn with Discovery Studio 5 software. This initial
structure was then saved as PDB file (appendix A) which consists atom types and Cartesian
coordinates of atoms that form lipidoid molecule. The lipidoid structure was chosen as C14113 which was developed and named by Love et. al.6 and shown in Figure 2 and the naming is
shown in figure 3. The next step was to build a system consists of several lipidoid molecules.
PACKMOL software package7 was used to put several lipidoid molecules into a volume without
overlapping. This was an important step because more than 20 molecules are needed to
observe a self-assembly behavior. Moreover, in order to observe an empty capsid
approximately 200 lipidoids are needed. It is not possible to place 200 lipidoid molecules into
a space without any overlapping by just creating different lipidoid molecules that have
different coordinates and then combining them manually. Sodium and acetate ions are
multiplied with same software. Solvation of the systems were done utilizing solvate plugin of
Visual Molecular Dynamics(VMD) software8.
Figure 2. C14-113 structure that has been used in MD simulations
Figure 3. Naming scheme of lipidoid structures4. The ones that start with C represents the tail group and others shows
head group of lipidoid.
2.1.2. MD Simulations
In order to perform MD simulations, apart from PDB file, a topology file which contains partial
charges and bonding information between atoms, and atom types, is needed. Bond
information was already known from the structure of the molecule. However, partial charges
were unknown. It is possible to calculate partial charges with ab-initio calculations. Since the
molecule is lipid-like, the partial charges were determined by correlating the atoms with
known lipid molecules instead of ab-initio method. The atom types were determined by same
method. The topology of neutral and protonated lipidoid molecules can be found in appendix
B.
NAMD9 software package was used for MD simulations. CHARMM27 parameter set were
chosen since the atom types were selected from CHARMM27 lipid topology file. There are
three main different simulation systems. They are:
Only uncharged lipidoids with water
Uncharged lipidoids with water and sodium acetate ions
Protonated lipidoids with water and sodium acetate ions
2.1.3. Steered MD Calculations
Steered MD methodology and Jarzynskis Equality10 was used for calculation of free energy of
one lipidoid to dissociation from a cluster. Jarzynski proved the equation which provides a
relationship between equilibrium free energy differences and work done via nonequilibrium
processes. The equality is
exp() = exp()
Where is
, with k is Boltzmann constant, is free energy difference and W is work done.
The work was applied to the system with Steered MD simulations which were done with SMD
package of NAMD software. For the small systems SMD simulation were done with 0.0001
A/ps constant speed and 20 kcal/mol/2 spring constant and for 1ns long. SMD with this setup
was done nine times in order to use irreversible work results within the Jarzynskis Equality to
calculate potential of mean force. Cluster structures were taken from five nanoseconds long
MD simulations of 20 lipidoid systems. Different water box sizes, velocity and spring constant
values were used and the most promising results were calculated with above values.
2.2.
Dissipative Particle Dynamics
In DPD simulations, group of particles are defined as a bead and instead of calculating every
interaction between atoms, the bead is treated as one particle. The atoms consisting of the
bead are not important, the only thing that is needed is the interaction parameter of the bead
itself which is calculated from an all atom simulation. The interaction parameters give the
force acting on a bead at a time step. The beads on the same molecule are connected to each
other with a spring. The force fi is sum of three pairwise additive components.
Where the summation is over all particles within cutoff radius. The first component is
conservative forces, the second is dissipative forces and the third one is a random force to
maintain system temperature. The dissipative and random forces total effect is a thermostat.
Thus, only conservative force component is related with the system chemistry.
where aij is maximum repulsion between particles.

By Flory-Huggins mean field theory and Flory-Huggins interaction parameter , the aij can be
calculated for DPD simulations.
Where Vm is the average molar volume, is the Hildebrand solubility parameter11, kB is

Boltzmann constant.
can be calculated with this equation.
For molecules that have strong interactions like hydrogen bonding, should be calculated
using Emix, instead of Ecoh.
where A and B represent the pure components and mix defines their blends, A and B are the
volume fractions of the pure components in the mixture12.
Groot and Warren11 showed that aii =25kbT and aij = aii +3.27 for a box density of 3 DPD units.
2.2.1. Interaction Parameter Calculations

Before starting calculations, first I decided the bead types. While doing that, close molar
volume values were a criterion for me. I defined six bead types. Three of them construct
lipidoid molecule and other three are used as solvent. The first three are shown with following
figures.
C3H9N
Vm=85.3 3.0 cm3
Density: 0.692 0.06 g/cm3
C4H10O
Vm=92.0 3.0 cm3
C4H10
Vm=94.5 3.0 cm3
Other bead types are composed of only water (Bead D), water and sodium (Bead E), and only
acetate (Bead F) molecules.
The calculation of the cohesive energy density (CED) is done by Materials Studio 6.0. Then I
calculated the aij terms with the above mentioned equations. For interactions between A-B,
B-D, and B-E, Emix formula was used because these molecules can form hydrogen bonds
between themselves.
In order to calculate CED, two modules of Materials Studio are used. First one is the
Amorphous Cell module and the other one is Forcite module. Amorphous Cell module is used
in order to create the system to be simulated. Forcite module on the other hand, calculates
the simulation trajectory. After the simulation is performed with Forcite, then cohesive energy
density can be calculated with the same module. Default values and Compass force field were
used for these calculations. Also summation methods were Ewald for electrostatics and atom
based for van der Waals interactions.
Although I have worked hard on this part of the project, it was not that possible to use them.
Because DPD module of Materials Studio does not have any features to implement
electrostatic interactions. Mesocite module can do simulations with electrostatic interactions
but our system did not minimize when using electrostatics. Since there was not enough time
left to complete the project, I moved to next phase to design systems similar to lipidoid
system.
2.2.2. Parameter Space Scanning

In order to understand what type of interactions create this type of self-assembly behavior,
an arbitrary system was created. By mimicking the system that was observed in atomistic MD
simulations, it was decided that four different bead types are enough. They are named as A,
B, C, and D.
10
A The head group of our branched oligomer has 3 A beads

B The oligomer has four tails as in the lipidoid case. Every tail has same number of
B beads
S1 and S2 These beads represent two types of solvent molecule.
DPD cubic boxes of size 25 25 25 u3 are constructed with a density of = 3 DPD units,
where u is the cutoff radius. I started doing these simulations with short linear molecule and
after trial of several different interaction parameters, I extended the molecule and added
branches to that. Since a molecule has an interaction parameter aij =25 with itself, any value
below 25 means that beads like each other. The bigger interaction parameter means they
dislike
more.
The
spring
constant
is
chosen
as
4.0
for
consecutive beads in a chain. Simulations are done 20,000 DPD steps long.
3. Results
3.1.
MD Results
Tables below show number of atoms, initial volume, protonation status and IDs that are given
in order to enable reader check the systems easily.
3.1.1. NPT Systems
ID
A01
A02
A03
A04
A05
A06
A07
A08
Protonation Number of
Ensemble
Status
Lipidoids
NPT
NPT
NPT
NPT
NPT
NPT
NPT
NPT
no
no
no
no
no
no
yes
yes
100
200
200
400
100
200
50
100
Number
of Na+
Number of
Acetate-
0
0
0
0
400
800
150
300
0
0
0
0
400
800
200
400
Number of
water
molecules
78151
21450
109922
92509
122947
112677
49305
103024
Initial Volume
(3)
140x140x140
102x105x106
160x160x160
160x160x160
162x162x162
163x163x164
120x121x120
155x152x155
Table 1 MD simulation systems with NPT ensemble
The systems that consist of no ions (A01 to A04) directly formed a cluster. Since there is no
other molecule than other lipidoids and water, it was an expected behavior for lipidoids. When
the ions (A05-A06) and protonation sites are introduced, then the behavior changed
significantly. They still tend to form clusters but due to ions in the system, the clusters are
smaller. This shows that the ions helped lipidoids to minimize their energy even with smaller
clusters. Introducing protonation site on the N2 atom of the lipidoid molecules (A07-A08) did
not change the system behavior significantly compared to systems with salt. However, none
of these systems showed the desired behavior so that I started doing simulations with NVT
ensemble to analyze the effect of pressure change.
11
Figure 4. 10ns snapshot of A01 system
12
Figure 11. 5ns snapshot from A08 system
3.1.2. NVT Systems

ID
Ensemble
B01
B02
B03
B04
B05
NVT
NVT
NVT
NVT
NVT
Protonation Number of
Status
Lipidoids
no
no
no
no
no
100
200
200
200
300
Number
of Na+
Number of
Acetate-
400
800
800
800
1200
400
800
800
800
1200
Table 2 MD simulations with NVT ensemble
Number of
water
molecules
14878
30819
66565
88067
80287
Volume (3)
95x95x95
120x120x120
140x140x140
132x147x160
155x155x155
13
As it can be seen from below figures lipidoids in NVT systems where V is constant, tends to
create a curvature and as number of lipidoids increase the curvature also gets bigger, towards
creating an empty sphere. However, I could not increase the number of lipidoids further
because the system B05 took 1.4 days/ns and minimum 5 ns simulation was needed to
observe the self-assembly behavior. These systems have average pressures negative so it can
be concluded that in NPT systems, the lipidoids cannot create a curvature because there is
always 1 atm pressure that is pushing the molecules. When the pressure is not constant,
molecules align themselves and by reducing pressure in the systems create a spherical
conformation.
Figure 12. First (Left) and 10 ns (Right) snapshots of B01 system.
Figure 13. First (Left) and 10 ns (Right) snapshots of B02 system.
14
Figure 14. Last snapshots of the 200 lipidoids system with more water molecules. (B03 on the left and B04 on the right)
Figure 15. First (Left) and 5ns (Right) snapshots of B05 system.
3.1.3. Steered MD results

Small systems are chosen to start SMD simulations. First, 20 lipidoids systems with charged
and uncharged lipidoids are run for 5 ns to see formation of clusters. After the system formed
clusters, biggest cluster is taken for SMD simulation. Charged cluster has nine lipidoids and
uncharged cluster has 12 lipidoids. One of the lipidoid on the surface of the cluster is chosen
and pulled from the cluster. PMF results are 20.31 kcal/mol and 23.42 kcal/mol for charged
and uncharged clusters respectively. It is observed that in the case of charged lipidoids PMF is
smaller but it is not a significant difference. Also they have different number of lipidoids which
can also affect PMF so that it is possible to say that protonating a lipidoid particle did not affect
the stability of the system significantly. However, since these are very small systems there is
the possibility of dominance of van der Waals interactions over electrostatic interactions.
Investigation of bigger systems are required for significance results.
15
3.2.
DPD Results
Interaction parameters of beads are shown in table 3.
Molar Volume(cm3)
A
B
C
D
E
F
A
9.86
85.30
25.00
B
12.46
92.00
17.57
25.00
C
8.28
94.50
26.24
33.99
25.00
D
23.50
90.35
115.22
155.23
143.24
25.00
E
38.51
90.35
423.19
216.84
491.57
137.48
25.00
F
40.11
57.00
384.55
339.61
448.86
137.27
26.04
25.00
Table 3. DPD interaction parameters
The resulting images for parameter space scanning show that which type of interactions and
concentrations affects the self-assembly mechanism. In order to create an interface between
two solvent groups, the approach was to make tail of the oligomer like one solvent, and head
of the molecule like other solvent. However, it is not only parameter needed to observe the
interface. The number of oligomers in the system and interactions between the different
solvent beads are also important. By systematically changing these parameters, I could design
a system that shows similar behavior to lipidoid system that I analyzed with MD methods by
forming a sphere around one solvent and leaving the other solvent distributed outside of that
sphere.
I started this process with an oligomer that is similar to C14-113 molecule. It has four tails with
six type B beads and has three type A beads in the head group. Chemical formula for this
oligomer can be written as A3B24.
The images on the left show isosurface which was created with density of head group of
oligomer. The images on the right show everything in the system. Head groups are shown in
red, tails are shown in green, solvent 1 molecules are shown in blue and solvent 2 molecules
are shown in pink. In some figures, solvents are not shown to emphasize the distribution of
oligomers. Since different systems have different interaction parameters and number of
molecules, every figure shows the number of molecules the system has and it has a table that
shows aij values.
I have started parameter space scanning with the system in fig. 16. By decreasing interaction
parameters with oligomer beads and solvent beads and by increasing number of lipidoid
molecules in the system I designed a system that shows similar behavior as I observed.
16
Interaction
Parameters
A
B
S1
S2
S1
30
100
25
100
S2
100
30
100
25
Number of oligomers:103
Number of solvent 1:22060
Figure 16. Initial system. Two solvents created two different layers and oligomers are distributed within the interface.
Interaction
Parameters
A
B
S1
S2
S1
30
100
25
100
S2
100
30
100
25
Figure 17. More oligomers with same parameters on previous figure (fig. 16). Oligomers are still placed themselves on the
interface but S2 beads preferred forming cylinder.
17
Interaction
Parameters
A
B
S1
S2
S1
12
100
25
100
S2
100
12
100
25
Figure 18. Only the interaction parameters have been changed from initial system. A and S1 like each other, B and S2 like
each other. Oligomers formed bilayer.
Interaction
Parameters
A
B
S1
S2
S1
12
100
25
100
S2
100
12
100
25
Figure 19. More oligomers than the system in fig. 18. S1 beads formed cylinder. S2 beads are distributed among tails of the
oligomers.
18
Interaction
Parameters
A
B
S1
S2
S1
12
100
25
50
S2
100
12
50
25
Figure 20. Same system with previous figure. S1 and S2 beads like each other more. S1 beads formed several cylinders.
Interaction
Parameters
A
B
S1
S2
S1
12
100
25
50
S2
100
12
50
25
Figure 21. By increasing the number of oligomers in the system more than 500, they formed spherical structure and S1
beads placed themselves in this sphere.
The rest of the systems while doing above design steps are shown in appendix C. I did not
include them here because they are intermediate steps. What I have found with this process
is that when the head group and tail groups like different solvent molecules, if there are
enough number of oligomers in the system, they form a capsid around the solvent molecules
19
which have attraction to head group. This is the same type of behavior we want when using
lipidoid molecules to transport siRNA.
4. Conclusion and future work
Although one of the objective of the project was to understand how these lipidoids form a
capsid around siRNA molecule, it does not seem possible to model that kind of big system.
Even though my biggest system that show spherical alignment have 300 lipidoids, it was not a
full capsid. So it needs more than 300 lipidoids to completely form a capsid around a siRNA
molecule. It is not feasible to work on a system that requires so much computational power
and time.
DPD simulations of lipidoid system could not be done due to electrostatic interactions. In long
time, Materials Studio or any other DPD capable software should be investigated to run DPD
simulations with this system.
The design principles that can separate two solvents with a sphere, can be investigated
further. Increase in the tail length, different number of tails can give us different behaviors. In
order to mimic the transportation of siRNA molecule, a new type of molecule can be
introduced and a system that can form a capsid around this molecule with one of the solvents
can be design.
20
5. References
1.
Barros, S. A. & Gollob, J. A. Safety profile of RNAi nanomedicines. Advanced Drug

Delivery Reviews 64, 17301737 (2012).
2.
Whitehead, K. a, Langer, R. & Anderson, D. G. Knocking down barriers: advances in

siRNA delivery. Nat. Rev. Drug Discov. 8, 12938 (2009).
3.
Zhao, J. & Feng, S.-S. Nanocarriers for delivery of siRNA and co-delivery of siRNA and
other therapeutic agents. Nanomedicine (Lond). 10, 2199228 (2015).
4.
Love, K. T. et al. Lipid-like materials for low-dose, in vivo gene silencing. Proc. Natl.
Acad. Sci. U. S. A. 107, 18649 (2010).
5.
San Diego: Accelrys Software Inc. Discovery Studio Modeling Environment, Release
3.5. Accelrys Software Inc. (2012).
6.
Love, K. T. et al. Correction for Love et al., Lipid-like materials for low-dose, in vivo
gene silencing. Proc. Natl. Acad. Sci. 107, 99159915 (2010).
7.
Martinez, L., Andrade, R., Birgin, E. G. & Mart??nez, J. M. PACKMOL: A package for
building initial configurations for molecular dynamics simulations. J. Comput. Chem.
30, 21572164 (2009).
8.
Humphrey, W., Dalke, A. & Schulten, K. VMD: Visual molecular dynamics. J. Mol.
Graph. 14, 3338 (1996).
9.
Phillips, J. C. et al. Scalable molecular dynamics with NAMD. Journal of Computational

Chemistry 26, 17811802 (2005).
10.
Park, S., Khalili-Araghi, F., Tajkhorshid, E. & Schulten, K. Free energy calculation from
steered molecular dynamics simulations using Jarzynskis equality. J. Chem. Phys. 119,
3559 (2003).
11.
Groot, R. D. & Warren, P. B. Dissipative Particle Dynamics: Bridging the Gap between
Atomistic and Mesoscopic Simulation. J. Chem. Phys. 107, 4423 (1997).
12.
Furuncuolu zaltn, T., Aviyente, V., Atlgan, C. & Demirel, L. Multiscale modeling of
poly(2-isopropyl-2-oxazoline) chains in aqueous solution. Eur. Polym. J. (2016).
doi:10.1016/j.eurpolymj.2016.10.013
21
6. Appendix
Appendix A
PDB file for one lipidoid molecule
ATOM
1 H95 UNK A 1
30.648 31.136 48.563 1.00 0.00
O1 H
ATOM
2 H93 UNK A 1
32.254 30.556 49.059 1.00 0.00
O1 H
ATOM
3 H94 UNK A 1
31.396 31.760 50.052 1.00 0.00
O1 H
ATOM
4 H92 UNK A 1
30.464 28.852 49.589 1.00 0.00
O1 H
ATOM
5 H91 UNK A 1
29.611 30.045 50.579 1.00 0.00
O1 H
ATOM
6 H90 UNK A 1
31.620 30.209 52.098 1.00 0.00
O1 H
ATOM
7 H89 UNK A 1
32.466 29.034 51.083 1.00 0.00
O1 H
ATOM
8 H88 UNK A 1
30.798 27.272 51.672 1.00 0.00
O1 H
ATOM
9 H87 UNK A 1
29.930 28.416 52.709 1.00 0.00
O1 H
ATOM
10 H86 UNK A 1
31.936 28.704 54.153 1.00 0.00
O1 H
ATOM
11 H85 UNK A 1
32.913 27.750 53.038 1.00 0.00
O1 H
ATOM
12 H84 UNK A 1
32.525 26.373 54.889 1.00 0.00
O1 H
ATOM
13 H83 UNK A 1
31.561 25.701 53.574 1.00 0.00
O1 H
ATOM
14 H82 UNK A 1
29.469 26.593 54.605 1.00 0.00
O1 H
ATOM
15 H81 UNK A 1
30.410 27.451 55.833 1.00 0.00
O1 H
ATOM
16 H80 UNK A 1
31.371 25.262 56.628 1.00 0.00
O1 H
ATOM
17 H79 UNK A 1
30.377 24.396 55.450 1.00 0.00
O1 H
ATOM
18 H78 UNK A 1
28.299 25.131 56.629 1.00 0.00
O1 H
ATOM
19 H77 UNK A 1
29.256 26.116 57.745 1.00 0.00
O1 H
ATOM
20 H76 UNK A 1
30.471 24.064 58.535 1.00 0.00
O1 H
ATOM
21 H75 UNK A 1
29.505 23.061 57.446 1.00 0.00
O1 H
ATOM
22 H74 UNK A 1
27.437 23.601 58.698 1.00 0.00
O1 H
ATOM
23 H73 UNK A 1
28.312 24.741 59.733 1.00 0.00
O1 H
ATOM
24 H72 UNK A 1
29.772 22.912 60.587 1.00 0.00
O1 H
ATOM
25 H71 UNK A 1
28.958 21.738 59.541 1.00 0.00
O1 H
ATOM
26 H22 UNK A 1
27.597 23.241 61.847 1.00 0.00
O1 H
22
ATOM
27 H23 UNK A 1
26.153 22.602 60.249 1.00 0.00
O1 H
ATOM
28 H21 UNK A 1
29.435 21.548 62.416 1.00 0.00
O1 H
ATOM
29 H20 UNK A 1
28.519 20.331 61.554 1.00 0.00
O1 H
ATOM
30 C46 UNK A 1
31.262 30.857 49.434 1.00 0.00
O1 C
ATOM
31 C45 UNK A 1
30.614 29.728 50.244 1.00 0.00
O1 C
ATOM
32 C44 UNK A 1
31.468 29.323 51.454 1.00 0.00
O1 C
ATOM
33 C43 UNK A 1
30.929 28.164 52.311 1.00 0.00
O1 C
ATOM
34 C42 UNK A 1
31.895 27.841 53.463 1.00 0.00
O1 C
ATOM
35 C41 UNK A 1
31.626 26.558 54.268 1.00 0.00
O1 C
ATOM
36 C40 UNK A 1
30.401 26.549 55.197 1.00 0.00
O1 C
ATOM
37 C39 UNK A 1
30.404 25.296 56.092 1.00 0.00
O1 C
ATOM
38 C38 UNK A 1
29.278 25.194 57.136 1.00 0.00
O1 C
ATOM
39 C37 UNK A 1
29.476 23.980 58.060 1.00 0.00
O1 C
ATOM
40 C36 UNK A 1
28.419 23.800 59.163 1.00 0.00
O1 C
ATOM
41 C35 UNK A 1
28.797 22.662 60.128 1.00 0.00
O1 C
ATOM
42 C11 UNK A 1
27.792 22.331 61.249 1.00 0.00
O1 C
ATOM
43 C10 UNK A 1
28.403 21.248 62.162 1.00 0.00
O1 C
ATOM
44 O3 UNK A 1
26.561 21.853 60.700 1.00 0.00
O1 O
ATOM
45 H121 UNK A 1
40.342 30.801 64.284 1.00 0.00
O1 H
ATOM
46 H122 UNK A 1
39.510 30.338 65.788 1.00 0.00
O1 H
ATOM
47 H123 UNK A 1
38.608 30.401 64.252 1.00 0.00
O1 H
ATOM
48 H120 UNK A 1
40.905 28.436 64.883 1.00 0.00
O1 H
ATOM
49 H119 UNK A 1
40.008 28.497 63.358 1.00 0.00
O1 H
ATOM
50 H118 UNK A 1
37.883 27.933 64.592 1.00 0.00
O1 H
ATOM
51 H117 UNK A 1
38.790 27.863 66.112 1.00 0.00
O1 H
ATOM
52 H116 UNK A 1
40.202 26.005 65.203 1.00 0.00
O1 H
ATOM
53 H115 UNK A 1
39.304 26.039 63.683 1.00 0.00
O1 H
ATOM
54 H114 UNK A 1
38.075 25.426 66.440 1.00 0.00
O1 H
ATOM
55 H113 UNK A 1
38.638 24.202 65.300 1.00 0.00
O1 H
23
ATOM
56 H112 UNK A 1
36.934 24.929 63.620 1.00 0.00
O1 H
ATOM
57 H111 UNK A 1
36.347 26.178 64.728 1.00 0.00
O1 H
ATOM
58 H110 UNK A 1
35.773 24.438 66.426 1.00 0.00
O1 H
ATOM
59 H109 UNK A 1
36.387 23.169 65.360 1.00 0.00
O1 H
ATOM
60 H108 UNK A 1
34.593 23.631 63.701 1.00 0.00
O1 H
ATOM
61 H107 UNK A 1
34.000 24.987 64.673 1.00 0.00
O1 H
ATOM
62 H106 UNK A 1
33.501 23.466 66.573 1.00 0.00
O1 H
ATOM
63 H105 UNK A 1
34.166 22.086 65.687 1.00 0.00
O1 H
ATOM
64 H104 UNK A 1
32.341 22.231 64.005 1.00 0.00
O1 H
ATOM
65 H103 UNK A 1
31.703 23.689 64.781 1.00 0.00
O1 H
ATOM
66 H102 UNK A 1
31.242 22.433 66.875 1.00 0.00
O1 H
ATOM
67 H101 UNK A 1
31.991 20.979 66.212 1.00 0.00
O1 H
ATOM
68 H100 UNK A 1
29.558 20.772 66.176 1.00 0.00
O1 H
ATOM
69 H99 UNK A 1
30.230 20.700 64.550 1.00 0.00
O1 H
ATOM
70 H98 UNK A 1
29.503 23.037 64.104 1.00 0.00
O1 H
ATOM
71 H124 UNK A 1
28.601 22.974 66.745 1.00 0.00
O1 H
ATOM
72 H97 UNK A 1
27.037 22.768 64.117 1.00 0.00
O1 H
ATOM
73 H96 UNK A 1
27.158 21.508 65.336 1.00 0.00
O1 H
ATOM
74 C60 UNK A 1
39.575 30.132 64.707 1.00 0.00
O1 C
ATOM
75 C59 UNK A 1
39.915 28.662 64.448 1.00 0.00
O1 C
ATOM
76 C58 UNK A 1
38.872 27.694 65.023 1.00 0.00
O1 C
ATOM
77 C57 UNK A 1
39.207 26.216 64.769 1.00 0.00
O1 C
ATOM
78 C56 UNK A 1
38.200 25.215 65.361 1.00 0.00
O1 C
ATOM
79 C55 UNK A 1
36.816 25.179 64.689 1.00 0.00
O1 C
ATOM
80 C54 UNK A 1
35.891 24.157 65.363 1.00 0.00
O1 C
ATOM
81 C53 UNK A 1
34.497 24.002 64.737 1.00 0.00
O1 C
ATOM
82 C52 UNK A 1
33.623 23.041 65.559 1.00 0.00
O1 C
ATOM
83 C51 UNK A 1
32.233 22.740 64.980 1.00 0.00
O1 C
ATOM
84 C50 UNK A 1
31.399 21.871 65.936 1.00 0.00
O1 C
24
ATOM
85 C49 UNK A 1
30.039 21.388 65.393 1.00 0.00
O1 C
ATOM
86 C48 UNK A 1
29.044 22.481 64.937 1.00 0.00
O1 C
ATOM
87 C47 UNK A 1
27.662 21.915 64.442 1.00 0.00
O1 C
ATOM
88 O4 UNK A 1
28.853 23.468 65.953 1.00 0.00
O1 O
ATOM
89 N3 UNK A 1
27.734 20.870 63.414 1.00 0.00
O1 N
ATOM
90 C8 UNK A 1
26.490 20.099 63.244 1.00 0.00
O1 C
ATOM
91 C7 UNK A 1
26.221 19.107 64.395 1.00 0.00
O1 C
ATOM
92 N2 UNK A 1
25.025 18.279 64.206 1.00 0.00
O1 N
ATOM
93 C9 UNK A 1
25.128 17.328 63.100 1.00 0.00
O1 C
ATOM
94 C6 UNK A 1
24.512 17.678 65.433 1.00 0.00
O1 C
ATOM
95 C5 UNK A 1
25.418 16.651 66.174 1.00 0.00
O1 C
ATOM
96 N1 UNK A 1
24.669 15.444 66.565 1.00 0.00
O1 N
ATOM
97 H15 UNK A 1
25.180 17.858 62.136 1.00 0.00
O1 H
ATOM
98 H16 UNK A 1
24.232 16.688 63.064 1.00 0.00
O1 H
ATOM
99 H17 UNK A 1
26.004 16.661 63.171 1.00 0.00
O1 H
ATOM 100 H14 UNK A 1
26.564 19.522 62.307 1.00 0.00
O1 H
25.613 20.762 63.114 1.00 0.00
O1 H
26.096 19.677 65.332 1.00 0.00
O1 H
27.124 18.482 64.540 1.00 0.00
O1 H
23.550 17.197 65.176 1.00 0.00
O1 H
ATOM 105 H9 UNK A 1
24.230 18.497 66.120 1.00 0.00
O1 H
ATOM 106 H8 UNK A 1
25.916 17.125 67.037 1.00 0.00
O1 H
ATOM 107 H7 UNK A 1
26.251 16.364 65.512 1.00 0.00
O1 H
9.720 10.780 70.720 1.00 0.00
O1 H
10.941 10.173 71.864 1.00 0.00
O1 H
10.353 11.851 71.992 1.00 0.00
O1 H
11.406 12.418 69.795 1.00 0.00
O1 H
11.930 10.743 69.580 1.00 0.00
O1 H
13.397 10.925 71.609 1.00 0.00
O1 H
25
12.855 12.589 71.861 1.00 0.00
O1 H
13.834 13.223 69.607 1.00 0.00
O1 H
14.409 11.566 69.407 1.00 0.00
O1 H
15.849 11.772 71.423 1.00 0.00
O1 H
15.223 13.394 71.745 1.00 0.00
O1 H
16.221 14.262 69.655 1.00 0.00
O1 H
16.752 12.644 69.184 1.00 0.00
O1 H
18.293 12.495 71.089 1.00 0.00
O1 H
17.697 14.006 71.775 1.00 0.00
O1 H
18.587 15.267 69.774 1.00 0.00
O1 H
19.180 13.747 69.093 1.00 0.00
O1 H
20.630 13.395 71.108 1.00 0.00
O1 H
20.069 14.931 71.789 1.00 0.00
O1 H
21.097 16.179 69.885 1.00 0.00
O1 H
21.543 14.651 69.113 1.00 0.00
O1 H
23.019 14.066 71.042 1.00 0.00
O1 H
22.484 15.501 71.910 1.00 0.00
O1 H
24.612 16.042 71.208 1.00 0.00
O1 H
23.572 16.968 70.138 1.00 0.00
O1 H
ATOM 133 H4 UNK A 1
25.625 16.013 69.082 1.00 0.00
O1 H
25.457 13.982 70.251 1.00 0.00
O1 H
ATOM 135 H6 UNK A 1
23.171 14.709 67.824 1.00 0.00
O1 H
ATOM 136 H5 UNK A 1
23.360 16.452 67.823 1.00 0.00
O1 H
ATOM 137 C34 UNK A 1
10.628 11.055 71.281 1.00 0.00
O1 C
11.744 11.520 70.342 1.00 0.00
O1 C
13.054 11.833 71.080 1.00 0.00
O1 C
14.182 12.336 70.165 1.00 0.00
O1 C
15.466 12.686 70.933 1.00 0.00
O1 C
16.572 13.295 70.058 1.00 0.00
O1 C
26
17.893 13.490 70.818 1.00 0.00
O1 C
18.969 14.266 70.044 1.00 0.00
O1 C
20.275 14.407 70.838 1.00 0.00
O1 C
21.402 15.138 70.091 1.00 0.00
O1 C
22.710 15.117 70.898 1.00 0.00
O1 C
23.904 15.938 70.362 1.00 0.00
O1 C
ATOM 149 C3 UNK A 1
24.709 15.392 69.157 1.00 0.00
O1 C
ATOM 150 C4 UNK A 1
23.931 15.506 67.832 1.00 0.00
O1 C
ATOM 151 O1 UNK A 1
25.088 14.030 69.359 1.00 0.00
O1 O
26.249 20.501 53.398 1.00 0.00
O1 H
27.007 18.914 53.118 1.00 0.00
O1 H
27.629 19.987 54.398 1.00 0.00
O1 H
24.826 18.691 54.382 1.00 0.00
O1 H
25.452 19.752 55.651 1.00 0.00
O1 H
27.281 18.090 56.139 1.00 0.00
O1 H
26.647 17.020 54.880 1.00 0.00
O1 H
24.481 16.807 56.139 1.00 0.00
O1 H
25.087 17.917 57.376 1.00 0.00
O1 H
26.960 16.308 57.892 1.00 0.00
O1 H
26.305 15.170 56.705 1.00 0.00
O1 H
24.194 14.962 58.023 1.00 0.00
O1 H
24.750 16.212 59.146 1.00 0.00
O1 H
26.714 14.736 59.775 1.00 0.00
O1 H
26.052 13.449 58.756 1.00 0.00
O1 H
23.980 13.374 60.162 1.00 0.00
O1 H
24.544 14.770 61.088 1.00 0.00
O1 H
26.558 13.398 61.842 1.00 0.00
O1 H
25.840 11.978 61.067 1.00 0.00
O1 H
23.814 12.193 62.546 1.00 0.00
O1 H
27
24.458 13.706 63.190 1.00 0.00
O1 H
26.450 12.423 64.121 1.00 0.00
O1 H
25.725 10.925 63.549 1.00 0.00
O1 H
25.388 11.240 65.962 1.00 0.00
O1 H
23.860 11.094 65.098 1.00 0.00
O1 H
ATOM 177 H1 UNK A 1
23.818 12.726 66.967 1.00 0.00
O1 H
22.860 14.379 65.540 1.00 0.00
O1 H
ATOM 179 H3 UNK A 1
26.015 13.795 66.793 1.00 0.00
O1 H
ATOM 180 H2 UNK A 1
25.686 14.313 65.142 1.00 0.00
O1 H
26.712 19.635 53.898 1.00 0.00
O1 C
25.752 18.995 54.903 1.00 0.00
O1 C
26.352 17.780 55.625 1.00 0.00
O1 C
25.401 17.145 56.650 1.00 0.00
O1 C
26.023 15.967 57.415 1.00 0.00
O1 C
25.099 15.387 58.496 1.00 0.00
O1 C
25.771 14.321 59.372 1.00 0.00
O1 C
24.890 13.870 60.546 1.00 0.00
O1 C
25.596 12.942 61.548 1.00 0.00
O1 C
24.752 12.712 62.811 1.00 0.00
O1 C
25.479 11.936 63.923 1.00 0.00
O1 C
24.717 11.772 65.264 1.00 0.00
O1 C
ATOM 193 C1 UNK A 1
24.165 13.036 65.961 1.00 0.00
O1 C
ATOM 194 C2 UNK A 1
25.208 14.146 66.122 1.00 0.00
O1 C
ATOM 195 O2 UNK A 1
23.017 13.478 65.225 1.00 0.00
O1 O
Appendix B1
Topology file for protonated lipidoid
RESI UNK
28
!Group RIGHTT1
Atom H95
HAL3 0.053
Atom H93
HAL3 0.053
Atom H94
HAL3 0.053
Atom H92 HAL2
0.053
Atom H91 HAL2
0.053
Atom H90 HAL2
0.053
Atom H89 HAL2
0.053
Atom H88 HAL2
0.053
Atom H87
HAL2 0.053
Atom H86
HAL2 0.053
Atom H85
HAL2 0.053
Atom H84
HAL2 0.053
Atom H83
HAL2 0.053
Atom H82
HAL2 0.053
Atom H81
HAL2 0.053
Atom H80
HAL2 0.053
Atom H79
HAL2 0.053
Atom H78
HAL2 0.053
Atom H77
HAL2 0.053
Atom H76
HAL2 0.053
Atom H75
HAL2 0.053
Atom H74
HAL2 0.053
Atom H73
HAL2 0.053
Atom H72 HAL2
0.053
Atom H71
HAL2 0.053
Atom H22
HAL1 0.053
Atom H23
HOL
Atom H21
HAL2 0.053
0.41
29
Atom H20
HAL2 0.053
Atom C46
CTL3
-0.159
Atom C45
CTL2
-0.106
Atom C44
CTL2
-0.106
Atom C43
CTL2
-0.106
Atom C42
CTL2
-0.106
Atom C41
CTL2
-0.106
Atom C40
CTL2
-0.106
Atom C39
CTL2
-0.106
Atom C38
CTL2
-0.106
Atom C37
CTL2
-0.106
Atom C36
CTL2
-0.106
Atom C35
CTL2
-0.106
Atom C11
CTL1
0.107
Atom C10
CTL2
0.081
Atom O3
OHL
-0.57
bond C46 H95
C46 H94
C46 H93
bond C45 H92
C45 H91
C45 C44
bond C44 H90
C44 H89
C44 C43
bond C43 H88
C43 H87
C43 C42
bond C42 H86
C42 H85
C42 C41
bond C41 H84
C41 H83
C41 C40
bond C40 H82
C40 H81
C40 C39
bond C39 H80
C39 H79
C39 C38
bond C38 H78
C38 H77
C38 C37
bond C37 H76
C37 H75
C37 C36
C46 C45
30
bond C36 H74
C36 H73
C36 C35
bond C35 H72
C35 H71
C35 C11
bond C11 O3O3 H23

bond C10 H21
C11 H22
C10 H20
!Group RIGHTT2
Atom H121 HAL3 0.053

C10 N3
C11 C10
31

Atom H99
HAL2 0.053
Atom H98
HAL1 0.053
Atom H124 HOL
0.41
Atom H97
HAL2 0.053
Atom H96
HAL2 0.053
Atom C60
CTL3
-0.159
Atom C59
CTL2
-0.106
Atom C58
CTL2
-0.106
Atom C57
CTL2
-0.106
Atom C56
CTL2
-0.106
Atom C55
CTL2
-0.106
Atom C54
CTL2
-0.106
Atom C53
CTL2
-0.106
Atom C52
CTL2
-0.106
Atom C51
CTL2
-0.106
Atom C50
CTL2
-0.106
Atom C49
CTL2
-0.106
Atom C48
CTL1
0.107
Atom C47
CTL2
0.081
Atom O4
OHL
-0.57
bond C60 H123
C60 H122
C60 H121
bond C59 H120
C59 H119
C59 C58
bond C58 H118
C58 H117
C58 C57
bond C57 H116
C57 H115
C57 C56
C60 C59
32
bond C56 H114
C56 H113
C56 C55
bond C55 H112
C55 H111
C55 C54
bond C54 H110
C54 H109
C54 C53
bond C53 H108
C53 H107
C53 C52
bond C52 H106
C52 H105
C52 C51
bond C51 H104
C51 H103
C51 C50
bond C50 H102
C50 H101
C50 C49
bond C49 H100
C49 H99
C49 C48
bond C48 O4O4 H124

bond C47 H97
C48 H98
C47 H96
!Group Head
Atom N2
NH3L -0.501
Atom C9
CTL5
0.028
Atom C7
CTL2
0.081
Atom C6
CTL2
0.081
Atom H15
HAL3 0.053
Atom H16
HAL3 0.053
Atom H17
HAL3 0.053
Atom H10
HAL2 0.053
Atom H9
HAL2 0.053
Atom H12
HAL2 0.053
Atom H11
HAL2 0.053
Atom H128 HCL
0.280
Atom N3
NTL
-0.248
Atom C8
CTL2
0.081
Atom C5
CTL2
0.081
C47 N3
C48 C47
33
Atom N1
NTL
Atom H14
HAL2 0.053
Atom H13
HAL2 0.053
Atom H8
HAL2 0.053
Atom H7
HAL2 0.053
-0.248
bond N2 H128
bond N3 C8
bond C8 H14
C8 H13 C8 C7
bond C7 H12 C7 H11
C7 N2
bond N2 C9 N2 C6
bond C9 H15 C9 H16 C9 H17
bond C6 H10
C6 H9 C6 C5
bond C5 H8 C5 H7 C5 N1
!Group LEFTT1
Atom H70
HAL3 0.053
Atom H69
HAL3 0.053
Atom H68
HAL3 0.053
Atom H67
HAL2 0.053
Atom H66
HAL2 0.053
Atom H65
HAL2 0.053
Atom H64
HAL2 0.053
Atom H63
HAL2 0.053
Atom H62
HAL2 0.053
Atom H61
HAL2 0.053
Atom H60
HAL2 0.053
Atom H59
HAL2 0.053
34
Atom H58
HAL2 0.053
Atom H57
HAL2 0.053
Atom H56
HAL2 0.053
Atom H55
HAL2 0.053
Atom H54
HAL2 0.053
Atom H53
HAL2 0.053
Atom H52
HAL2 0.053
Atom H51
HAL2 0.053
Atom H50
HAL2 0.053
Atom H49
HAL2 0.053
Atom H48
HAL2 0.053
Atom H47
HAL2 0.053
Atom H46
HAL2 0.053
Atom H4
HAL1 0.053
Atom H18
HOL
Atom H6
HAL2 0.053
Atom H5
HAL2 0.053
Atom C34
CTL3
-0.159
Atom C33
CTL2
-0.106
Atom C32
CTL2
-0.106
Atom C31
CTL2
-0.106
Atom C30
CTL2
-0.106
Atom C29
CTL2
-0.106
Atom C28
CTL2
-0.106
Atom C27
CTL2
-0.106
Atom C26
CTL2
-0.106
0.41
35
Atom C25
CTL2
-0.106
Atom C24
CTL2
-0.106
Atom C23
CTL2
-0.106
Atom C3
CTL1
0.107
Atom C4
CTL2
0.081
Atom O1
OHL
-0.57
bond C34 H70
C34 H69
C34 H68
bond C33 H67
C33 H66
C33
bond C32 H65
C32 H64
C32 C31
bond C31 H63
C31 H62
C31 C30
bond C30
C30
C30
H61
H60
C32
C29
bond C29 H59
C29 H58
C29 C28
bond C28 H57
C28 H56
C28 C27
bond C27 H55
C27 H54
C27 C26
bond C26 H53
C26 H52
C26 C25
bond C25 H51
C25 H50
C25 C24
bond C24 H49
C24 H48
C24 C23
bond C23 H47 C23 H46 C23 C3

bond C3
O1
O1 H18
!Group LEFTT2

Atom H45
HAL2 0.053
Atom H44
HAL2 0.053
C3 H4 C3 C4
C34 C33
36
Atom H43
HAL2 0.053
Atom H42
HAL2 0.053
Atom H41
HAL2 0.053
Atom H40
HAL2 0.053
Atom H39
HAL2 0.053
Atom H38
HAL2 0.053
Atom H37
HAL2 0.053
Atom H36
HAL2 0.053
Atom H35
HAL2 0.053
Atom H34
HAL2 0.053
Atom H33
HAL2 0.053
Atom H32
HAL2 0.053
Atom H31
HAL2 0.053
Atom H30
HAL2 0.053
Atom H29
HAL2 0.053
Atom H28
HAL2 0.053
Atom H27
HAL2 0.053
Atom H26 HAL2
0.053
Atom H25
HAL2 0.053
Atom H24
HAL2 0.053
Atom H1 HAL1
0.053
Atom H19
HOL
0.41
Atom H3
HAL2 0.053
Atom H2
HAL2 0.053
Atom C61
CTL3
-0.159
Atom C22
CTL2
-0.106
Atom C21
CTL2
-0.106
Atom C20
CTL2
-0.106
37
Atom C19
CTL2
-0.106
Atom C18
CTL2
-0.106
Atom C17
CTL2
-0.106
Atom C16
CTL2
-0.106
Atom C15
CTL2
-0.106
Atom C14
CTL2
-0.106
Atom C13
CTL2
-0.106
Atom C12
CTL2
-0.106
Atom C1
CTL1
0.107
Atom C2
CTL2
0.081
Atom O2
OHL
-0.57
bond C61 H125
C61 H126
C61 H127 C61 C22
bond C22 H45
C22 H44
C22 C21
bond C21 H43 C21 H42 C21 C20

bond C20 H41
C20 H40
C20 C19
bond C19 H39
C19 H38
C19
C18
bond C18 H37 C18 H36
C18
C17
bond C17
H34
C17 C16
H35
C17
bond C16 H33
C16 H32
C16 C15
bond C15 H31
C15 H30
C15 C14
bond C14 H29
C14 H28
C14 C13
bond C13 H27
C13 H26
C13 C12
bond C12 H25
C12 H24
C12 C1
bond C1 O2 O2
H19
H1
C1
C1 C2
38
RESI ACE
-1.00 ! acetate, from CTER, from top_all27_prot_lipid_na.inp
GROUP
ATOM C1 CT3 -0.27 !
H21 O1
ATOM H1 HA
0.09 !
| //
ATOM H2 HA
0.09 ! H22--C1--C2
ATOM H3 HA
0.09 !
| \
ATOM C2 CC
0.34 !
H23 O2(-)
ATOM O1 OC
-0.67
ATOM O2 OC
-0.67
BOND C1 C2 C2 O2
BOND C1 H1 C1 H2 C1 H3
DOUBLE C2 O1
IMPR C2 C1 O2 O1
ACCEPTOR O1 C2
ACCEPTOR O2 C2
PATCHING FIRST NONE LAST NONE
RESI SOD
1.00 ! Sodium Ion
GROUP
ATOM SOD SOD 1.00
END
Appendix B2
Topology file for neutral lipidoid
RESI UNK
!Group RIGHTT1
Atom H95
HAL3 0.053
Atom H93
HAL3 0.053
39
Atom H94
HAL3 0.053
Atom H92 HAL2
0.053
Atom H91 HAL2
0.053
Atom H90 HAL2
0.053
Atom H89 HAL2
0.053
Atom H88 HAL2
0.053
Atom H87
HAL2 0.053
Atom H86
HAL2 0.053
Atom H85
HAL2 0.053
Atom H84
HAL2 0.053
Atom H83
HAL2 0.053
Atom H82
HAL2 0.053
Atom H81
HAL2 0.053
Atom H80
HAL2 0.053
Atom H79
HAL2 0.053
Atom H78
HAL2 0.053
Atom H77
HAL2 0.053
Atom H76
HAL2 0.053
Atom H75
HAL2 0.053
Atom H74
HAL2 0.053
Atom H73
HAL2 0.053
Atom H72 HAL2
0.053
Atom H71
HAL2 0.053
Atom H22
HAL1 0.053
Atom H23
HOL
Atom H21
HAL2 0.053
Atom H20
HAL2 0.053
Atom C46
CTL3
0.41
-0.159
40
Atom C45
CTL2
-0.106
Atom C44
CTL2
-0.106
Atom C43
CTL2
-0.106
Atom C42
CTL2
-0.106
Atom C41
CTL2
-0.106
Atom C40
CTL2
-0.106
Atom C39
CTL2
-0.106
Atom C38
CTL2
-0.106
Atom C37
CTL2
-0.106
Atom C36
CTL2
-0.106
Atom C35
CTL2
-0.106
Atom C11
CTL1
0.107
Atom C10
CTL2
0.081
Atom O3
OHL
-0.57
bond C46 H95
C46 H94
C46 H93
bond C45 H92
C45 H91
C45 C44
bond C44 H90
C44 H89
C44 C43
bond C43 H88
C43 H87
C43 C42
bond C42 H86
C42 H85
C42 C41
bond C41 H84
C41 H83
C41 C40
bond C40 H82
C40 H81
C40 C39
bond C39 H80
C39 H79
C39 C38
bond C38 H78
C38 H77
C38 C37
bond C37 H76
C37 H75
C37 C36
bond C36 H74
C36 H73
C36 C35
bond C35 H72
C35 H71
C35 C11
bond C11 O3O3 H23
C11 H22
C46 C45
C11 C10
41
bond C10 H21
C10 H20
!Group RIGHTT2

Atom H99
HAL2 0.053
C10 N3
42
Atom H98
HAL1 0.053
Atom H124 HOL
0.41
Atom H97
HAL2 0.053
Atom H96
HAL2 0.053
Atom C60
CTL3
-0.159
Atom C59
CTL2
-0.106
Atom C58
CTL2
-0.106
Atom C57
CTL2
-0.106
Atom C56
CTL2
-0.106
Atom C55
CTL2
-0.106
Atom C54
CTL2
-0.106
Atom C53
CTL2
-0.106
Atom C52
CTL2
-0.106
Atom C51
CTL2
-0.106
Atom C50
CTL2
-0.106
Atom C49
CTL2
-0.106
Atom C48
CTL1
0.107
Atom C47
CTL2
0.081
Atom O4
OHL
-0.57
bond C60 H123
C60 H122
C60 H121
bond C59 H120
C59 H119
C59 C58
bond C58 H118
C58 H117
C58 C57
bond C57 H116
C57 H115
C57 C56
bond C56 H114
C56 H113
C56 C55
bond C55 H112
C55 H111
C55 C54
bond C54 H110
C54 H109
C54 C53
C60 C59
43
bond C53 H108
C53 H107
C53 C52
bond C52 H106
C52 H105
C52 C51
bond C51 H104
C51 H103
C51 C50
bond C50 H102
C50 H101
C50 C49
bond C49 H100
C49 H99
C49 C48
bond C48 O4O4 H124

bond C47 H97
C48 H98
C47 H96
!Group Head
Atom N2
NTL
-0.561
Atom C9
CTL5
0.028
Atom C7
CTL2
0.081
Atom C6
CTL2
0.081
Atom H15
HAL3 0.053
Atom H16
HAL3 0.053
Atom H17
HAL3 0.053
Atom H10
HAL2 0.053
Atom H9
HAL2 0.053
Atom H12
HAL2 0.053
Atom H11
HAL2 0.053
Atom N3
NTL
-0.561
Atom C8
CTL2
0.081
Atom C5
CTL2
0.081
Atom N1
NTL
-0.561
Atom H14
HAL2 0.053
Atom H13
HAL2 0.053
C47 N3
C48 C47
44
Atom H8
HAL2 0.053
Atom H7
HAL2 0.053
bond N3 C8
bond C8 H14 C8 H13 C8 C7
bond N2 C9 N2 C6
bond C9 H15 C9 H16 C9 H17
bond C6 H10 C6 H9 C6 C5
!Group LEFTT1
Atom H70
HAL3 0.053
Atom H69
HAL3 0.053
Atom H68
HAL3 0.053
Atom H67
HAL2 0.053
Atom H66
HAL2 0.053
Atom H65
HAL2 0.053
Atom H64
HAL2 0.053
Atom H63
HAL2 0.053
Atom H62
HAL2 0.053
Atom H61
HAL2 0.053
Atom H60
HAL2 0.053
Atom H59
HAL2 0.053
Atom H58
HAL2 0.053
Atom H57
HAL2 0.053
Atom H56
HAL2 0.053
Atom H55
HAL2 0.053
45
Atom H54
HAL2 0.053
Atom H53
HAL2 0.053
Atom H52
HAL2 0.053
Atom H51
HAL2 0.053
Atom H50
HAL2 0.053
Atom H49
HAL2 0.053
Atom H48
HAL2 0.053
Atom H47
HAL2 0.053
Atom H46
HAL2 0.053
Atom H4
HAL1 0.053
Atom H18
HOL
Atom H6
HAL2 0.053
Atom H5
HAL2 0.053
Atom C34
CTL3
-0.159
Atom C33
CTL2
-0.106
Atom C32
CTL2
-0.106
Atom C31
CTL2
-0.106
Atom C30
CTL2
-0.106
Atom C29
CTL2
-0.106
Atom C28
CTL2
-0.106
Atom C27
CTL2
-0.106
Atom C26
CTL2
-0.106
Atom C25
CTL2
-0.106
Atom C24
CTL2
-0.106
Atom C23
CTL2
-0.106
Atom C3
CTL1
0.107
0.41
46
Atom C4
CTL2
0.081
Atom O1
OHL
-0.57
bond C34 H70
C34 H69
C34 H68
bond C33 H67
C33 H66
C33
bond C32 H65
C32 H64
C32 C31
bond C31 H63
C31 H62
C31 C30
bond C30
C30
C30
H61
H60
C32
C29
bond C29 H59
C29 H58
C29 C28
bond C28 H57
C28 H56
C28 C27
bond C27 H55
C27 H54
C27 C26
bond C26 H53
C26 H52
C26 C25
bond C25 H51
C25 H50
C25 C24
bond C24 H49
C24 H48
C24 C23
bond C23 H47 C23 H46 C23 C3

bond C3
O1
O1 H18
!Group LEFTT2

Atom H45
HAL2 0.053
Atom H44
HAL2 0.053
Atom H43
HAL2 0.053
Atom H42
HAL2 0.053
Atom H41
HAL2 0.053
Atom H40
HAL2 0.053
C3 H4 C3 C4
C34 C33
47
Atom H39
HAL2 0.053
Atom H38
HAL2 0.053
Atom H37
HAL2 0.053
Atom H36
HAL2 0.053
Atom H35
HAL2 0.053
Atom H34
HAL2 0.053
Atom H33
HAL2 0.053
Atom H32
HAL2 0.053
Atom H31
HAL2 0.053
Atom H30
HAL2 0.053
Atom H29
HAL2 0.053
Atom H28
HAL2 0.053
Atom H27
HAL2 0.053
Atom H26 HAL2
0.053
Atom H25
HAL2 0.053
Atom H24
HAL2 0.053
Atom H1 HAL1
0.053
Atom H19
HOL
0.41
Atom H3
HAL2 0.053
Atom H2
HAL2 0.053
Atom C61
CTL3
-0.159
Atom C22
CTL2
-0.106
Atom C21
CTL2
-0.106
Atom C20
CTL2
-0.106
Atom C19
CTL2
-0.106
Atom C18
CTL2
-0.106
Atom C17
CTL2
-0.106
Atom C16
CTL2
-0.106
48
Atom C15
CTL2
-0.106
Atom C14
CTL2
-0.106
Atom C13
CTL2
-0.106
Atom C12
CTL2
-0.106
Atom C1
CTL1
0.107
Atom C2
CTL2
0.081
Atom O2
OHL
-0.57
bond C61 H125
C61 H126
C61 H127 C61 C22
bond C22 H45
C22 H44
C22 C21
bond C21 H43 C21 H42 C21 C20

bond C20 H41
C20 H40
C20 C19
bond C19 H39
C19 H38
C19
C18
bond C18 H37 C18 H36
C18
C17
bond C17
H34
C17 C16
H35
C17
bond C16 H33
C16 H32
C16 C15
bond C15 H31
C15 H30
C15 C14
bond C14 H29
C14 H28
C14 C13
bond C13 H27
C13 H26
C13 C12
bond C12 H25
C12 H24
C12 C1
bond C1 O2 O2
H19
H1
C1
C1 C2
RESI ACE
-1.00 ! acetate, from CTER, from top_all27_prot_lipid_na.inp
GROUP
ATOM C1 CT3 -0.27 !
ATOM H1 HA
0.09 !
H21 O1
| //
49
ATOM H2 HA
0.09 ! H22--C1--C2
ATOM H3 HA
0.09 !
| \
ATOM C2 CC
0.34 !
H23 O2(-)
ATOM O1 OC
-0.67
ATOM O2 OC
-0.67
BOND C1 C2 C2 O2
BOND C1 H1 C1 H2 C1 H3
DOUBLE C2 O1
IMPR C2 C1 O2 O1
ACCEPTOR O1 C2
ACCEPTOR O2 C2
RESI SOD
1.00 ! Sodium Ion
GROUP
ATOM SOD SOD 1.00
END
Appendix C
Systems that have been observed during parameter space scanning.
50
Interaction
Parameters
A
B
S1
S2
S1
12
100
25
100
S2
100
12
100
25
Interaction
Parameters
A
B
S1
S2
S1
30
100
25
50
S2
100
30
50
25
51
Interaction
Parameters
A
B
S1
S2
S1
30
50
25
30
S2
50
30
30
25
Interaction
Parameters
A
B
S1
S2
S1
30
100
25
50
S2
100
30
50
25
52
Interaction
Parameters
A
B
S1
S2
S1
30
50
25
50
S2
50
30
50
25
Number of oligomers: 348

Number of solvent 1: 18750

#034 Rational Nanocarrier Design Principles For Lipid-Like Compounds

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

#034 Rational Nanocarrier Design Principles For Lipid-Like Compounds

Uploaded by

Copyright:

Available Formats

1

ENS 491-492 Project Final Report

#034 Rational Nanocarrier Design Principles for Lipid-like

Figure 1. siRNA transportation with lipidoid molecules3

Figure 2. C14-113 structure that has been used in MD simulations

, with k is Boltzmann constant, is free energy difference and W is work done.

Dissipative Particle Dynamics

where aij is maximum repulsion between particles.

Where Vm is the average molar volume, is the Hildebrand solubility parameter11, kB is

can be calculated with this equation.

2.2.1. Interaction Parameter Calculations

2.2.2. Parameter Space Scanning

A The head group of our branched oligomer has 3 A beads

Table 1 MD simulation systems with NPT ensemble

Figure 4. 10ns snapshot of A01 system

Figure 6. 12ns snapshot of A03 system

Figure 5. 5ns snapshot of A02 system

Figure 7. 10ns snapshot of A04 system

Figure 8. 10ns snapshot of A05 system

Figure 10. 5ns snapshot of A07 system

Figure 9. 2ns snapshot of A06 system

Figure 11. 5ns snapshot from A08 system

3.1.2. NVT Systems

Table 2 MD simulations with NVT ensemble

Figure 12. First (Left) and 10 ns (Right) snapshots of B01 system.

Figure 13. First (Left) and 10 ns (Right) snapshots of B02 system.

3.1.3. Steered MD results

Interaction parameters of beads are shown in table 3.

Table 3. DPD interaction parameters

Barros, S. A. & Gollob, J. A. Safety profile of RNAi nanomedicines. Advanced Drug

Whitehead, K. a, Langer, R. & Anderson, D. G. Knocking down barriers: advances in

Phillips, J. C. et al. Scalable molecular dynamics with NAMD. Journal of Computational

30.648 31.136 48.563 1.00 0.00

32.254 30.556 49.059 1.00 0.00

31.396 31.760 50.052 1.00 0.00

30.464 28.852 49.589 1.00 0.00

29.611 30.045 50.579 1.00 0.00

31.620 30.209 52.098 1.00 0.00

32.466 29.034 51.083 1.00 0.00

30.798 27.272 51.672 1.00 0.00

29.930 28.416 52.709 1.00 0.00

31.936 28.704 54.153 1.00 0.00

32.913 27.750 53.038 1.00 0.00

32.525 26.373 54.889 1.00 0.00

31.561 25.701 53.574 1.00 0.00

29.469 26.593 54.605 1.00 0.00

30.410 27.451 55.833 1.00 0.00

31.371 25.262 56.628 1.00 0.00

30.377 24.396 55.450 1.00 0.00

28.299 25.131 56.629 1.00 0.00

29.256 26.116 57.745 1.00 0.00

30.471 24.064 58.535 1.00 0.00

29.505 23.061 57.446 1.00 0.00

27.437 23.601 58.698 1.00 0.00

28.312 24.741 59.733 1.00 0.00

29.772 22.912 60.587 1.00 0.00

28.958 21.738 59.541 1.00 0.00

27.597 23.241 61.847 1.00 0.00

26.153 22.602 60.249 1.00 0.00

29.435 21.548 62.416 1.00 0.00

28.519 20.331 61.554 1.00 0.00

31.262 30.857 49.434 1.00 0.00