Molecular docking is a method for predicting how two molecules, such as a ligand and its protein target, will interact and fit together in three dimensions. Docking has become an important tool in drug discovery for identifying potential binding conformations between drug candidates and protein targets. The key steps in a typical docking workflow involve selecting the receptor and ligand molecules, then using software to computationally predict the orientation of binding and evaluate the fit through scoring functions. Popular molecular docking software packages include AutoDock, GOLD, and Glide. Applications of docking include virtual screening in drug discovery and lead optimization.

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AMITY INSTITUTE OF PHARMACY
AMITY UNIVERSITY UTTAR PRADESH
LUCKNOW
2018-20
TYPES AND SCREENING OFTYPES AND SCREENING OF
DOCKINGDOCKING

2. Amity Institute of PharmacyWhat Is Docking….?
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• Docking is a method which predicts the preferred orientation of one molecule to
a second when bound to form a stable complex with overall minimum energy.
• Docking attempts to find the “best” matching between two molecules

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Why is docking important?
• It is of extreme relevance in cellular biology
• It is the key to rational drug design
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Docking
Rational Design Of
Drugs
Prediction of the
binding affinity
(Scoring Function)
Identification of the ligand’s
correct binding Geometry
(pose) in the binding Site
(Binding Mode)

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Docking can be between
•Protein - Ligand
•Protein – Protein
•Protein – Nucleotide
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A Typical Docking Workflow
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Receptor selection Ligand selection
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Key Stages In Docking

7. Amity Institute of PharmacyTypes of docking
1. Rigid Docking (Lock and Key)
• In rigid docking, the internal geometry of both the receptor and ligand are treated
as rigid.
2. Flexible Docking (Induced fit)
• An enumeration on the rotations of one of the molecules (usually smaller one) is
performed. Every rotation the energy is calculated; later the most optimum pose is
selected.
3. Manual docking
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8. Amity Institute of PharmacyManual docking
Dock or fit a molecule in the binding site
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Binding group on the ligand and binding site are known, defined by the
operator.
Binding group in the ligand is paired with its complementary group in the binding site
Ideal bonding distance for potential interaction is defined.
Docking procedure is started
The program try to get best fit, as defined by the operator

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The paired groups are not directly overlaid, they are , fitted within preferred bonding
distance
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Both ligand and protein remain same conformation throughout the process
So this is a rigid fit, once a molecule successfully docked fit optimization is carried out.
Same as in energy minimization
Different conformation of molecule can be docked to in same way
Identify the best fit

10. Amity Institute of PharmacySoftware's
• SANJEEVINI – IIT Delhi (www.scfbio-iitd.res.in/sanjeevini/sanjeevini.jsp)
• GOLD – University of Cambridge ,UK
(www.ccdc.cam.ac.uk/Solutions/GoldSuite/Pages/GOLD.aspx)
• AUTODOCK - Scripps Research Institute,USA (autodock.scripps.edu/)
• GemDock (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/)
• Hex Protein Docking - University of Aberdeen, UK (hex.loria.fr/)
• GRAMM (Global Range Molecular Matching) Protein docking - A Center for
• Bioinformatics, University of Kansas, USA
(www.bioinformatics.ku.edu/files/vakser/gramm/) 10

11. Amity Institute of PharmacyApplications
• 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 protein target of interest.
• Drug Discovery (lead optimization) docking can be used to predict in 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.
• Bioremediation Protein ligand docking can also be used to predict pollutants
that can be degraded by enzymes.
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• Docking- the process by which molecular modeling software fits a molecule
into target binding sites.
• Used for finding binding modes of protein with ligands/inhibitors
• In molecular docking, attempt to predict the structure of the intermolecular
complex formed between two or more molecules.
Molecular docking tries to predict the structure of the intermolecular complex
formed between two or more constituent molecules.
Molecular docking has become an increasingly important tool for drug
discovery.
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Docking based screening
1) Virtual based screening
2) Molecular based screening
Molecular based screening

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IN-silico generation of ligands(using chemsketch in this software we can draw
the structure of Ligand/molecule).
Conversion of file format( OPEN BABEL is the software used to converting
format of file .mol to .pdb
Protein optimization(RCSB- protein data bank, here you can prepare your protein
of interest for docking).
Energy Minimization( here SPDV swiss-Pdb viewer software) This can be done
by commanding.
Molecular docking (creation of .gpf-grid parameter file and .dpf-dock parameter
file. Autodock Vina, Autodock 4.0, Autodock 4.2 13
Steps Involve in
molecular docking

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This are the software used to make auto griding and dock parameters along with
grid mapping.
Running the docking algorithm(CYGWIN-1 in this software we will create GLG
file and DLG file here this software works commanding after getting succesfull
comand for auto grid(glg) and auto dock (dlg)
After this step we got to know minimal binding energy CYGWIN-2
Hydrogen bond analysis( UCSF CHIMERA we use this software for visulisation
and analysis of result.
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ADMET( the molecules which have shown H bond with the active site residue or
any other residue of the binding pocket note down those molecules and then run
these molecule on the online ADMET serve.
Applications
1. Structure based drug design.
2. Lead Optimization.
3. Virtual Screening.
4. Protein-Protein Docking.
5. Chemical mechanism studies.
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Virtual Screening
• The process of drug discovery has been reorganize with the development of
genomics, proteomics, bioinformatics and efficient technologies like
combinatorial chemistry, high throughput screening, virtual screening, de novo
design, in vitro, in silico screening and structure-based drug design.
• Virtual screening has emerged as a reliable, cost-effective and time-saving
technique for the discovery of lead compounds.
• The virtual screening approach for docking small molecules into a known
protein structure is a powerful tool for drug design that has become an integral
part of the drug discovery process in recent years.
• Based on molecule modeling and computational analysis of chemical data
those compounds should be identified that are relevant for certain biological
receptor.

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Any virtual screening method faces two critical issues:
 docking, that is how the virtual ligand interacts with the receptor
 scoring, that is how the quality of the designed structure is estimated
The main steps are:
(1) Identify and determine the structure of the receptor.
(2) Suggest a set of potential ligands that bound the receptor based on
theoretical principles and experimental data.
(3) Determine the structure of the receptor-ligand that leads to successful
bound with a minimum energy levels.
(4) Repeat steps (2) and (3) in order to improve the receptor-ligand interaction.
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Methods for virtual
Screening

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