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Lab Report 2 BME 310

This document summarizes a student's laboratory experiment on molecular docking. The student used various software tools including AutoDock Vina, AutoDock Tools, and PyMOL to perform molecular docking simulations. The student analyzed the binding interactions between a ligand and receptor protein, identified 6 binding modes with varying binding affinities and structural alignments, and concluded that molecular docking can provide insights to aid drug discovery and bioscience research.

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Can Mungan
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29 views8 pages

Lab Report 2 BME 310

This document summarizes a student's laboratory experiment on molecular docking. The student used various software tools including AutoDock Vina, AutoDock Tools, and PyMOL to perform molecular docking simulations. The student analyzed the binding interactions between a ligand and receptor protein, identified 6 binding modes with varying binding affinities and structural alignments, and concluded that molecular docking can provide insights to aid drug discovery and bioscience research.

Uploaded by

Can Mungan
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as DOCX, PDF, TXT or read online on Scribd
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,

Faculty of Biomedical Engineering

BME310
2023-2024

Experiment #2:
Molecular Docking

Name Surname
Can Mungan
Student ID
20160612031
Abstract
A computational method called molecular docking is used to mimic the binding
interaction between a ligand and a receptor molecule. In this laboratory experiment,
molecular docking was carried out and the results were shown using AutoDock Vina,
AutoDock Tools, and PyMOL. Analysis of the crystal structures of the c-Alb kinase
domain in association with small-molecule inhibitors and imatinib was the major goal.

1. Introduction
The study of drug development and structural biology greatly benefits from the
computer technique known as molecular docking. It entails forecasting a ligand's
preferred shape and binding affinity within the active site of a macromolecular target,
usually a protein. Stable ligand-receptor complexes are created through the
investigation of ligand conformations (sampling) and evaluation of their binding
potencies (scoring). There are various molecular docking techniques; some assume the
target as rigid while others take into account the conformational flexibility of both the
ligand and the receptor. Scoring functions calculate the free energy of binding while
using deterministic and stochastic procedures. High complexity of the issue, a variety of
docking strategies, and the requirement for customized scoring functions for particular
ligand-receptor interactions, including carbohydrate-protein binding, provide difficulties.
A crucial tool for drug design, lead optimization, and the investigation of molecular
interactions in various biological systems is molecular docking, which is frequently used
in concert with other computational and experimental techniques. In order to visualize
the data, the research used AutoDock Vina as the main tool, which was supplemented
by other software tools as AutoDock Tools and PyMOL.
Materials & Methods
 AutoDock Vina
 AutoDock Tools
 Protein in PDB (Protein Data Bank) format
 Ligand
 PyMOL
Experiment Steps:
 Software Setup
 Download the "vina" file and unzip it to the desktop.
Add Hydrogens to Protein Structure
 Open AutoDockTools.
 Load the protein structure in PDB format (protein.pdb).
 Add hydrogens to the protein using Edit > Hydrogens > Add > Polar Only.
Define the Search Space (Grid)
 Create a grid box for the docking process using Grid > Grid Box.
 Configure the grid options:
 Number of points in x_dimension = 22
 Number of points in y_dimension = 24
 Number of points in z_dimension = 28
 Spacing (angstrom): 1.000
 Center grid box:
 x_center: 11
 y_center: 90.5
 z_center: 57.5
Load Ligand
 Load the ligand (ligand.pdb) using Ligand > Input > Open.
Torsion Tree Setup
 Hide the protein structure to visualize the ligand better.
 Set up rotatable bonds in the ligand using Ligand > Torsion Tree > Choose
Torsions > Click Done.

Save Ligand Structure


 Save the ligand structure in PDBQT format in the "vina" directory (ligand.pdbqt).
Configuration File for AutoDock Vina
 Open a command prompt (cmd).
 Navigate to the "vina" directory.
 Copy the Vina directory link from Program Files (x86): "C:\Program Files (x86)\
The Scripps Research Institute\Vina\vina.exe".
 Create a configuration file (conf.txt) with the following contents:
 makefileCopy code
 receptor = protein.pdbqt
ligand = ligand.pdbqt
center_x = 11
center_y = 90.5
center_z = 57.5
size_x = 22
size_y = 24
size_z = 28
Run AutoDock Vina
 Run AutoDock Vina using the command:
 cCopy code
 "C:\Program Files (x86)\The Scripps Research Institute\Vina\vina.exe" --config
conf.txt --log log.txt
 This command performs the docking simulations and generates binding modes.
Visualize the Results
 Examine the docking results by opening the output file (ligand_out) in PyMOL.
 Also, open the receptor file (protein.pdb) in PyMOL to compare the results.

2. Results

Figure 1 To convert the protein and ligand files to the pdb format, we used Autodocktool to load them into the "vina" file.

Figure 2 Using the ligand's provided grid options


Figure 3 Protein.pdb and ligand.pdb files were converted to.pdbqt format and stored in the "vina" file.

Figure 4 The "vina" file directory has been modified, and conf.txt has been added.
Figure 5 CMD was used for the analysis.

Figure 6 Viewing the outcomes with PyMOL


3. Discussion
Mode 1 displays a highly effective binding interaction with a -13.0 kcal/mol
affinity. The RMSD data show that the structural alignment with both reference postures
(1.b and u.b) is almost perfect.
According to the RMSD value, Mode 2 exhibits a significantly lower binding
affinity and a moderate structural divergence from the reference poses. Mode 3 has a
decreased affinity and observable structural aberrations, which point to a relatively
weaker binding relationship.
The structural alignment and moderate binding affinity of Mode 4 point to a
moderate binding interaction. According to Mode 5's moderate binding affinity and little
structural variations, the binding association is reasonably stable. When compared to
one set of references, Mode 6 exhibits a moderate binding affinity and great structural
alignment, although there are considerable structural differences (u.b.).
Lower negative affinities in this sample correspond to more robust binding
interactions. Mode 1 is a strong candidate for further investigation in the field of drug
discovery due to its exceptional performance in terms of both high affinity and perfect
structural alignment.
The affinities are waning, and the structural variances are rising in modes 2 to 5.
Mode 6 raises questions while displaying good alignment with one set of references due
to significant structural variances with another set of references.
Insights concerning each mode's potential as a therapeutic candidate are
crucially gleaned from its binding affinity and structural correctness. When assessing
their appropriateness for additional research, careful thought is required.
4. Conclusion
Using AutoDock Vina and PyMOL, we successfully carried out molecular docking
simulations in this laboratory experiment.
We learned more about the binding interactions between the ligand and the
receptor by specifying the search space and setting the docking parameters. Drug
development and other research fields benefit greatly from the insights provided by
molecular docking, which also has potential uses in the realm of bioscience.
5. Reference
 Morris, G. M., Huey, R., & Olson, A. J. (2008). Using AutoDock for ligand-
receptor docking. Current Protocols in Bioinformatics, 24(1), 8.14.1-8.14.54.

 Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and
accuracy of docking with a new scoring function, efficient optimization, and
multithreading. Journal of Computational Chemistry, 31(2), 455-461.

 Leach, A. R., & Shoichet, B. K. (2006). Peishoff, molecular docking. Annual


Review of Biophysics and Biomolecular Structure, 35, 333-359.

 Kitchen, D. B., Decornez, H., Furr, J. R., & Bajorath, J. (2004). Docking and
scoring in virtual screening for drug discovery: methods and applications. Nature
Reviews Drug Discovery, 3(11), 935-949.

 Shoichet, B. K., & Kuntz, I. D. (1991). Protein docking and complementarity.


Journal of Molecular Biology, 221(1), 327-346.

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