It was an assignment to submit for the completion of the drug design project offered by Red-Green Research Centre (RGRC), Bangladesh.

1. Report On
QUANTUM COMPUTATION AND MOLECULAR DOCKING
Submitted By
Syed Mohammad Lokman
M.Sc., Department of Genetic Engineering and Biotechnology
University of Chittagong, Chittagong-4331, Bangladesh

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Acknowledgment
I would like to thank Red-Green Research Centre, Chittagong and Professor Mohammad A. Halim for
arranging such an impactful course. Special thanks to all the trainer for their tremendous support
throughout the course.
I am grateful to my teacher and mentor Md. Mahbub Hasan and Dr. Adnan Mannan for guiding me
as always to have skills on computer aided drug designing.

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i. Contents
Acknowledgment ...................................................................................................................................2
i. Contents...............................................................................................................................................3
ii. Figures.................................................................................................................................................4
iii. Tables.................................................................................................................................................4
A. Quantum Computation......................................................................................................................5
1.1 3D Structure Drawing...................................................................................................................5
1.2 Molecular Optimization and Frequency Calculation...................................................................5
2.1 Optimized Drug Image .................................................................................................................6
2.2 Imaginary Frequency Check.........................................................................................................7
3.1 Bond Distance...............................................................................................................................7
3.2 Bond Angle ...................................................................................................................................8
4.1 HOMO, LUMO Energy Values.......................................................................................................8
4.2 Energy gap of HOMO and LUMO .................................................................................................8
5. Optimized Drug (Butoconazole) Parameters.................................................................................8
6. HOMO and LUMO orbital image....................................................................................................9
B. Molecular Docking ...........................................................................................................................10
1. Protein Preparation and Optimization........................................................................................10
2. Molecular Docking........................................................................................................................10
3.1 Non-bolding Interactions ...........................................................................................................10
3.2 Picture of Interaction .................................................................................................................11
4. 1 Designing Five Structure of Aurein 1.2 Peptide .......................................................................12
4.2 Docking of Five Models against Protein (PDB: 3IBD)................................................................12
4.3 PatchDock Non-bonding Interaction Image..............................................................................13

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ii. Figures
Figure 1: Butoconazole drawn in GaussView 5.0.8.................................................................................5
Figure 2: Performing Molecular Optimization and Frequency Calculation ............................................5
Figure 3: Semi-empirical/ PM6 level of theory was selected for the calculation...................................6
Figure 4: A typical view of performing calculations in Gaussian ............................................................6
Figure 5: Optimized 3D structure of Butoconazole ................................................................................6
Figure 6: Imaginary Frequency Check.....................................................................................................7
Figure 7: IR Spectrum confirmed no imaginary frequency.....................................................................7
Figure 8: Image of HOMO of Optimized Butoconazole ..........................................................................9
Figure 9: Image of LUMO of Optimized Butoconazole ...........................................................................9
Figure 10: Ligand (Butoconazole) docked with protein (PDB:3ibd)......................................................11
Figure 11: Non-bonding interaction between drug (Butoconazole) with amino acids (PDB:3ibd) ......11
Figure 12: Five model (a-e) of Aurein 1.2 peptide................................................................................12
Figure 13: Non-bonding Interaction of 5 peptide models (a-e)............................................................13
iii. Tables
Table 1: Bond Distance ...........................................................................................................................7
Table 2: Bond Angle ................................................................................................................................8
Table 3: Molecular Orbital Energy ..........................................................................................................8
Table 4: Molecular Orbital Energy Gap (Between HOMO and LUMO)...................................................8
Table 5: Different Properties of Optimized Butoconazole......................................................................8
Table 6: Docking Grid Box Properties ...................................................................................................10
Table 7: Binding Energies Different Docked Pose.................................................................................10
Table 8: Five non-bond ineractions ......................................................................................................10
Table 9: Score, Area, and ACE of Models..............................................................................................12

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A. Quantum Computation
1.1 3D Structure Drawing
A 3D Structure of Butoconazole was drawn in GaussView 5.0.8.
Figure 1: Butoconazole drawn in GaussView 5.0.8
1.2 Molecular Optimization and Frequency Calculation
The 3D structure of Butoconazole was selected for preforming molecular optimization and frequency
calculation in gas phase using Semi-empirical/ PM6 level of theory. The video of the drawing 3D
structure and performing optimization and frequency calculation will be found at
https://youtu.be/M7p8SkudrBE
Figure 2: Performing Molecular Optimization and Frequency Calculation

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Figure 3: Semi-empirical/ PM6 level of theory was selected for the calculation
Figure 4: A typical view of performing calculations in Gaussian
2.1 Optimized Drug Image
Figure 5: Optimized 3D structure of Butoconazole

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2.2 Imaginary Frequency Check
From the “Gaussian Calculation Summery” tab, imaginary frequency was checked, and it was shown
zero that means no imaginary frequency. IR Spectrum also confirmed that there was no imaginary
frequency.
Figure 6: Imaginary Frequency Check
Figure 7: IR Spectrum confirmed no imaginary frequency
3.1 Bond Distance
Three selective bond distances were shown in Table:1.
Table 1: Bond Distance
Atoms Bond Distance
22Cl-3C 1.7259381
11C-25S 1.7573602
24Cl-16C 1.7249443

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3.2 Bond Angle
Three selective bond angles were shown in Table:2.
Table 2: Bond Angle
Atoms Bond Angle
22Cl-3C-2C 119.0218824
11C-25S-9C 38.4787342
24Cl-16C-15C 116.7923357
4.1 HOMO, LUMO Energy Values
The HOMO and LUMO energy values were listed in Table:3.
Table 3: Molecular Orbital Energy
Molecular Orbital Energy
LUMO+2 -0.0103900000
LUMO+1 -0.0206800000
LUMO -0.0323300000
HOMO -0.3362300000
HOMO-1 -0.3447100000
HOMO-2 -0.3503000000
4.2 Energy gap of HOMO and LUMO
The energy gap between HOMO and LUMO were calculated and listed in Table:4.
Table 4: Molecular Orbital Energy Gap (Between HOMO and LUMO)
Molecular Orbital Energy Gap
ELUMO - EHOMO 0.3039
ELUMO+1 - EHOMO-1 0.32403
ELUMO+2 - EHOMO-2 0.33991
5. Optimized Drug (Butoconazole) Parameters
The electronic energy (E), enthalpy (H), Gibbs free energy (G), and dipole moment (Debye) of the
optimized Butoconazole were listed in Table:5.
Table 5: Different Properties of Optimized Butoconazole
Description Value
Electronic Energy (E) 0.405516
Enthalpy (H) 0.406460
Gibbs Free Energy (G) 0.319735
Dipole moment (Debye) 1.0265

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6. HOMO and LUMO orbital image
Figure 8: Image of HOMO of Optimized Butoconazole Figure 9: Image of LUMO of Optimized Butoconazole
The complete video of result analysis will be found at https://youtu.be/Ksnqo26yXO8.

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B. Molecular Docking
1. Protein Preparation and Optimization
The protein (PDB: 3ibd) was downloaded from RCSB PDB database and cleaned (removing water
molecule and other molecule than amino acid residues) in PyMol. Then the cleaned protein was
optimized using Swiss PDB Viewer to perform molecular docking with previously prepared ligand
Butoconazole. A whole video on protein molecule preparation and optimization will be found at
https://youtu.be/BHIx86f9VLQ.
2. Molecular Docking
Molecular docking between prepared Butoconazole and protein (PDB: 3ibd) was performed in
AutoDock Vina. The grid box coordinates were given in Table:6 and binding energies were listed in
Table:7. A full video on performing molecular docking and visualization will be found at
https://youtu.be/BHIx86f9VLQ.
Table 6: Docking Grid Box Properties
Properties Coordinates
Center
x = 20.2575
y = 11.0403
z = 24.348
Size
x = 60.1667110634
y = 65.2751292419
z = 66.7326102257
Table 7: Binding Energies Different Docked Pose
Ligand Binding Affinity rmsd/ub rmsd/lb
Butoconazole_Pose_1 -8.1 0 0
Butoconazole_Pose_2 -7.9 4.614 2.931
Butoconazole_Pose_3 -7.1 19.463 17.978
Butoconazole_Pose_4 -6.9 19.316 17.951
Butoconazole_Pose_5 -6.7 7.364 4.227
Butoconazole_Pose_6 -6.7 28.25 25.496
Butoconazole_Pose_7 -6.6 28.21 25.435
Butoconazole_Pose_8 -6.6 19.287 17.951
Butoconazole_Pose_9 -6.4 19.92 18.323
3.1 Non-bonding Interactions
Non-bonded interactions (5) between drug (Butoconazole) and protein amino acid residues
(PDB:3ibd) were listed in Table:8.
Table 8: Five non-bond interactions
Contacts Bond distances (Å) Contacts Bond distances (Å)
Pi···C-H (Val367) 3.85108 Pi···Alkyl (Cys436) 5.19437
Pi···Pi (Phe297) 4.96977 Pi···Alkyl (Val367) 4.7344
Alkyl···Alkyl (Val477) 3.74626

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3.2 Picture of Interaction
Figure 10: Ligand (Butoconazole) docked with protein (PDB:3ibd)
Figure 11: Non-bonding interaction between drug (Butoconazole) with amino acids (PDB:3ibd)

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4. 1 Designing Five Structure of Aurein 1.2 Peptide
Aurein 1.2 peptide (Sequence: GLFDIIKKIAESF) structure was predicted using PEP-FOLD 3.5. The best
five models were shown in Figure:12.
(a) (b) (c) (d) (e)
Figure 12: Five model (a-e) of Aurein 1.2 peptide
4.2 Docking of Five Models against Protein (PDB: 3IBD)
Docking of the five predicted Aurein 1.2 peptide models against protein (PDB: 3IBD) was performed
in PatchDock webtool and the Score, Area, and ACE of five models were listed in Table:9.
Table 9: Score, Area, and ACE of Models
Model Score Area ACE
Model1 7296 935.10 -51.18
Model2 7432 1061.60 -57.43
Model3 7676 948.50 -432.88
Model4 8260 1109.10 -137.95
Model5 7296 1056.40 -148.19

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4.3 PatchDock Non-bonding Interaction Image
The non-bonding interactions of five predicted model of Aurein 1.2 peptide were shown in Figure:13.
(a) (b)
(c) (d)
(e)
Figure 13: Non-bonding Interaction of 5 peptide models (a-e)