AIM - TO PERFORM THE STUDY AND PREPARE A REPORT

ON MOLECULAR DOCKING FOR DEVELOPMENT OF NEW

DRUG MOLECULES

INTRODUCTION :-

Molecular docking is an attractive scaffold receptor complex with optimized

to understand drugbiomolecular conformation and with the intention of
interactions for the rational drug design and possessing less binding free energy.
discovery, as well as in the mechanistic
Docking is an attempt to find the best
study by placing a molecule (ligand) into the
matching between two molecules.
preferred binding site of the target specific
region of the DNA/protein (receptor) mainly A more serious definition..Docking is a
in a non-covalent fashion to form a stable method which predicts the preferred
complex of potential efficacy and more orientation of one ligand when bound in an
specificity. The information obtained from active site to fom a stable complex.
the docking technique can be used to
suggest the binding energy, free energy and
stability of complexes. At present, docking
technique is utilized to predict the tentative
binding parameters of ligand-receptor
complex beforehand. The main objective of
molecular docking is to attain ligand-

 TYPES OF DOCKING :-

I) FLEXIBLE DOCKING - II) SEMI-FLEXIBLE DOCKING - III) RIGID DOCKING -

The general principle of In this approach, the ligand In rigid docking, the main
flexible docking is based molecule is the only geometry of the target and
on the induced-fit flexible element while the ligand is retained and
hypothesis offered by protein is rigid. In addition frozen during docking
Daniel Koshland in 1958. to the six translational and analysis. The basis of this
As a result, it is also rotational degrees of type of docking analysis is
known as “induced-fit freedom, the the ‘Lock and Key’
docking,” conformational degrees of hypothesis, proposed by
freedom of the ligand are Emil Fischer in 1894.
also tested.
  MOLECULAR DOCKING:-To achieve
an optimized conformation for both
receptor and ligand & the relative
orientation between protein and
ligand such that the free energy of
the overall system is minimized.
Successful docking methods search
high-dimensional spaces effectively
and use a scoring function that
correctly ranks candidate dockings.

 DIFFERENT TERMS USED IN DOCKING SYSTEM:-

• RECEPTOR/HOST/LOCK - • LIGAND/ GUEST/ KEY - • DOCKING - Computational

receiving molecule molecule bind to receptor - simulation of a candidate -
(protein) - large. small. preferred orientation of
ligand binding site to a
receptor.
 LOCK AND KEY

• Finding the correct relative orientation of

the "key' which will open up the "lock.

• On the surface of the lock is the key hole..

• In which direction to turn the key after it is

inserted..

 TYPES OF INTERACTIONS

• ELECTROSTATIC FORCES - • ELECTRODYNAMICS FORCES - • STERIC FORCES - These are

Forces with electrostatic The most widely known is caused by entropy. For
origin are due to the probably the van der Waals example, in cases where
charges residing in the interaction. entropy is limited, there
matter. may be forces to minimize
the free energy of the
system.
 PREPARATION DOCKING PARAMETER FILE

For the preparation of the docking parameter file (dpf), click on Docking > Macromolecule > Set rigid filament > Open in the ADT window to
open the target PDBQT. Similarly, ligand pdbqt can also be opened by clicking on Docking > Ligand > Open. Then, set the algorithm by
clicking on Docking > Search Parameters > Genetic algorithm and setting docking parameters. Finally, click on Docking > Output > Lararckian
GA and save it as a dpf file. Then ADT is ready to run. Firstly, it runs. It required a proper time and needed the grid parameter file as well as a
docking parameter file.
  SOFTWARES

I. SANJEEVANI – I|T Delhi (www.scfbio-itd.res.inlsanjeevinilsanjeevini,jsp)

II. GOLD- University of Cambridge UK

(www.ccdc.cam.ac.uk/Solutions/GoldSuite/Pages/GOLD.aspx)

III. AUTODOCK - Scripps Research Institute,USA (autodock.scripps.edu/)

IV. GEM DOCK(Generic Evolutionary Method for Molecular Docking) -A tool, developed by
Jinn-Moon Yang, a professor of the Institute of Bioinformatics, National Chiao Tung
University, Taiwan (gemdock.life.nctu.edu.tw/dock)

V. HEX PROTEIN DOCKING- University of Aberdeen, UK (hex.loria.ftr)

VI. GRAMM (Global Range Molecular Matching) Protein docking -A Center for
Bioinformatics, University of Kansas, USA
(www.bioinformatics.ku.edu/fles/vakser/lgramm/)

 APPLICATIONS

I. Virtual screening (hit identification) docking 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 the protein target of interest.

II. Drug Discovery (lead optimization) docking can be used to predict where and in which
relative orientation a ligand binds to a protein (binding mode or pose). This information
may in turn be used to design more potent and selective analogs.

III. Bioremediation Protein ligand docking can also be used to predict pollutants that can be
degraded by enzymes.

 ANALYSIS OF DOCKING RESULT

ADT also offers to evaluate docking interactions and binding energies of a minimum of ten
conformations along with a docking inhibition constant (Ka). By selecting Analyze > Docking >
Open, you may view the findings by opening the dlg file. A popup will open, click “OK” and then
further click Analyze > Conformation > Play > & > Show info.

 CONCLUSION - It can be employed to identify a lead molecule against a protein target or in

contrary it can be employed to identify protein target against a query ligand. It can further be
employed for de novo design of the lead molecule against a disease-causing protein target.

 RESULT - THE STUDY OF MOLECULAR DOCKING FOR DEVELOPMENT OF NEW DRUG MOLECULES
WERE STUDIED AND REPORTED.