This document discusses molecular docking and drug receptor interactions. It introduces molecular docking as a structure-based technique to understand drug interactions for rational drug design. There are different types of docking including rigid docking which keeps molecules fixed, and flexible docking which allows some movements. Common docking tools are described along with basic steps like preparing proteins and ligands, running docking algorithms, and analyzing results such as hydrogen bonding to identify potential drug candidates.

1. COMPUTER AIDED DRUG
DESIGN
MOLECULAR DOCKING AND DRUG
RECEPTOR INTERACTIONS: RIGID
DOCKING, FLEXIBLE DOCKING & EXTRA
PRECISION DOCKING
Presented by Sumit Maji
M.Pharm, Pharmaceutical Chemistry
Bharat Technology

2. CONTENT
 Introduction
 Molecular Docking
 Docking: Basic concepts
 Importance of Docking
 Flowchart of Docking
 Types of Molecular Docking
 Docking tools
 Drug Receptor Interactions

3. INTRODUCTION
 Docking is structure based technique which attempts to
find the best match between two molecules.
 Molecular docking is an attractive scaffold to understand
drug biomolecular interactions for the rational drug
design & drug discovery.

4. MOLECULAR DOCKING
 Molecular docking is an attempt to find the best
matching between two molecules. Docking is a method
which predicts the preferred orientation of one ligand
when bound in an active site to form a stable complex.
 Knowledge of the preferred orientation may be used to
predict he strength of association or binding affinity
between two molecules.

5. DOCKING: BASIC CONCEPTS
 The protein can be thought as the lock & ligand can be
thought as a key.

6. IMPORTANCE OF DOCKING
 Identification of the ligand’s correct binding geometry
(pose) in the binding site(Binding Mode)
 Prediction of the binding affinity (Scoring Function)
 Rational design of drugs: It is the key to rational drug
design. The result of docking can be used to find
inhibitors for specific target proteins and design of new
drugs as well.

7. FLOWCHART OF DOCKING

8. TYPES OF MOLECULAR DOCKING
 Rigid Docking(Lock & Key)
In rigid docking, internal geometry of both the receptor
and ligand is rigid/kept fixed, then docking is performed.
 Flexible Docking (Induced fit)
An enumeration on the rotations of one of the
molecules(usually smaller one) is performed. In every
rotation the energy is calculated. Then most optimum
pose is selected.

9. RIGID DOCKING
 Historically the first approaches
 Protein and ligand are fixed
 Search for the relative orientation of two
molecules with lowest energy.
 First apply steric constants to limit search space
and examine energetics of possible binding
conformaions.

10. FLEXIBLE DOCKING
 Protein ligand docking
 Flexible ligand and rigid receptor
 Search space much larger.
 Either reduce flexible ligand to rigid fragments
connected by one or several hinges, or search the
conformaional space using monte carlo methods or
molecular dynamics.

11. DOCKING TOOLS
Docking Software
DOCK
AutoDock
GOLD
GLIDE
LigandFit
Docking Algorithm
Shape fitting
Lamarckian algorithm
Genetic Algorithm
Monte Carlo Sampling

12. STEPS FOLLOWED FOR
MOLECULAR DOCKING
 IN-silico generation of ligands (Using chemsketch
we can draw the structure of ligand/molecule
 Converted the file to suitable format (OPEN BABEL
is the software used to converting format of file from
.mol to .pdb.
 Protein optimization( RCSB- Protein data bank,
here we can prepare our protein of interest for
docking).www.rcsb.org

13.  Energy minimization ( SPDV swiss-Pdb viewer
software)
 Molecular docking (creaion of .gpf-grid parameter
file & .dpf-dock parameter file.
1) Autodock Vina
2) Autodock 4.0
3) Autodock 4.2
This softwares are used to make auto griding and
dock parameters along with grid mapping.

14.  Running the docking algorithm(CYGWIN-1 in this
software we will create GLG file & DLG file here this
software works commanding after getting
successful command for auto grid(glg) & auto dock
(dlg)
 After this step we got to know minimal binding
energy CYGWIN-2
 Hydrogen bond analysis (UCSF CHIMERA software
is used for visulisation & analysis of result)

15.  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
servers

16. REFERENCES
 Morris GM, Goodsell DS, Halliday RS, Huey R, Hart
WE, Olson AJ(1998). ‘Automated docking using a
Lamarckian genetic algorithm and an emperical
binding free energy function’. Journal of
Computational Chemistry 19(14): 1639-1662.
 Morris RJ, Najmanovich RJ, Kahraman A, Thornton
JM(May,2005). ‘Real spherical harmonic expansion
coefficients as 3D shape descriptors for protein
binding pocket and ligand comparisons’.
Bioinformatics 21(10): 2347-55
 www.ncbi.nlm.nih.gov/pubmed/18446297