Molecular docking and it application ...

Bioinformatics -molecular docking

1. Molecular docking and its applications
Presented By,
C. Aarthi
123011356003
Ⅱ M.Sc Biotechnology

Submitted To,
Ms. P. Mala
Assistant Professor
Department of Biotechnology
PMIST

2. Content
•Introduction
•Overview
•Steps for flexible docking in AutoDock vina
•Software for structure based drug design and molecular docking
•Applications
•MCQ Question
•MCQ Answer
•References

3. Introduction
•Molecular docking is a method to predict the preferred orientation of one molecule to a
second when bound to each other to form a stable complex.
•Computers and programs are used to predict or simulate the possible reaction between two
molecules based on their three dimensional structures.
•Analyzing the interactions basically comes with 3D graphics which can be manipulated in
several ways to clearly explore in detail the interaction involved between the atoms in the
two interacting molecules.
•This method can therefore be used not only to predict possible binders or inhibitors, but
also to predict how strong the association between the molecules can be.
•It is useful to know the binding energy when you are comparing a group of compounds or
derivatives to determine which derivative is the best binder or inhibitor.

4. •Docking
Molecular docking consists of computational simulation through which it is possible to
predict interactions between two structures, which may be between a protein and a ligand
(molecule or drug) or between two proteins.

•Need to perform docking
A target molecule (protein or nucleic acid),a drug lead molecule and a computer program to
perform docking are the pre-recquisites for any rationale drug discovery project.




Overview

5. Target
•Target finding
Target finding and target validation itself is a money spinning area. Pharmaceutical
companies are racing to find out good and better targets from the human genome. Main
goals of the human genome project is the target discovery. There are various method by
which targets could be identified. Some of them are literature mining, genome mining,
Proteomics, Microarray etc..
•Target structure
Once the target is identified, the next step is to obtain its 3D molecular structure. The
structure of the target protein could be obtained by any one of these three methods: X-Ray
crystallography, NMR, Modelling.

6. Steps for flexible docking in AutoDock Vina
•Choose the protein target and ligand molecule.
•Carry out protein and ligand preparation.
•Select the docking site in protein.
•Carry out protein-ligand docking using docking tool.
•Different ligand poses are generated.

7. •RCSB PDB select the protein and download the PDB format.
•PubChem select the ligand and download the SDF format.
•Create the new file in desktop for docking.
•Open the AutoDock tool. Drag the protein drop it here. Delete all the water molecules
because of your pocket region that could not ligand easily comfortable in the pocket
region.
•Hydrogens will be added polar hydrogens only. Add charges in kollman charges. Now the
protein is prepared. Save the protein (Click the grid – macromolecule-choose).You can
see the new tab select protein – select molecule).
•Protein and ligand save the PDBQT format.

8. •Same as ligand drag and drop it here (PyMol)
•Download the PyMol visualization tool.we can convert the SDF format of ligand PDB
format.
• Save the file export molecule ligand PDB save this file. In the ligand file drag and drop
the AutoDock tools.
•Go to ligand –input- choose. Open the new tab select the ligand.
•Go to ligand –output-save in PDBQT format.
•Ligand to attach the protein PDBQT .Click on the grid-macromolecule-choose. New tab
open here. Again choose the protein select the molecule.
•Click on the grid - grid box. click on file-output grid dimension file. File name will be
grid. txt. change the length of grid box for x, y, z dimension.
•To perform the docking – config file-receptor protein-ligand-center X,YZ –size- energy
range- exhaustiveness. Close the AutoDock file.

9. •Search the command prompt- file name will be copy and paste-double dash receptor
protein.pdbqt-ligand ligand pdbqt-double dash- config.txt-output file.
•Copy and paste the word pad. Now output will be a Pdbqt file.
•Now open the PyMol – insert the protein structure.
•Output file drag and insert here.
•It will be 9 poses entire protein can be pocket site, binding score ,find out the ligands in
which interacting the pocket region .
•Performed the docking using AutoDock Vina

10. Software for structure based drug design and molecular
docking
•Affinity- Uses the energy of the ligand/receptor complex to automatically find the best
binding modes of the ligand to the receptor.
•Autodock -Designed to predict how small molecules such as substrates or drug candidates
bind to a receptor of a known 3D structure.
•Dock Vision- Docking package created by scientist for scientists by including MC,GA,
and database screening docking algorithms.
•FlexiDock- Simple , flexible docking of ligands into binding sites on protein.
•FlexX- Fast computer program for predicting protein-ligand interaction.
•HINT- Empirical molecular modelling system with new methods for de novo drug design
and protein or nucleic acid structural analysis.

11. •VEGA DOCK- Generates many possible orientations of a putative ligand within a user
selected region of a receptor structure.
•GRAMM-Global Range Molecular Matching. Requires only the atomic coordinates of the
two molecules to predict the complex structure.
•SITUS- Program package for modelling of atomic resolution structures into low
resolution density maps.
•LIGPLOT- Generates schematic diagrams of protein ligand interactions for a given PDB
file.
•ICM-Dock- Unique set of tools for accurate individual ligand-protein docking,
peptide-protein docking, and protein-protein docking, including interactive graphic tools.

12. Applications
•Docking could also used to study protein-protein interaction.
•Docking is used for structure based drug discovery where the binding efficiency of
particular drug is computationally tested by docking it with the known well studied target
structure.
•Bioremediation: protein ligand docking can also used to predict the putative pollutants
that can be degradable by the biodegradative proteins.
• Hit identification: Docking combined with a scoring function can be used to quickly
screen large databases of potential drugs in silico to identify molecules that are likely to
bind to protein target of interest.

13. MCQ Question
1.Which of the following software is used for molecular docking?
a)LUDI b)MEGA c)LIGPLOT d)CoMFA
2. How many types of molecular docking?
a)Four b)three c)two d)one
3.Protein-protein docking involves two protein molecules simulated by the
computer/computer program to bind/interact with one another?
a)true b)false
4. In case of Protein-ligand docking, __ ligands are often ___ in adapting their shape to fit
the receptor binding pocket. a) small molecule, highly flexible b) large molecule, highly
flexible c) large molecule, more flexible d) small molecule, less flexible

14. MCQ Answer
1.LIGPLOT
2.Two
3.True
4.Small molecule highly flexible

15. References
Bioinformatics Principles and Applications Zhumur Gosh and
Bibekanand Mallick April 2008 edition.

16. Thank you