COMPUTER

AIDED DRUG DESIGN

Session 2015-16
NEETIKA
SINGH
M.Sc. IV Semester

Content
Drug
Drug Discovery and time line
Drug Design
CADD
Basic Mechanism of CADD
Selection of Disease
Target Selection
Structure Determination
PDB
Selection of Ligands/ Drugs
Molecular Docking
VMD
Benefits of CADD

DRUG
A chemical substance that affects the
processes of the mind or body which
is used in
diagnosis
Treatment
prevention
of disease
or other abnormal
condition.

DRUG DISCOVERY
CYCLE

Drug discovery &

developmenttimeline

DRUG DESIGN
Drug design, is the inventive process
of finding new medications based on
the knowledge of a biological target.

DRUG
DESIGNING .........
Selected/designed
molecule
should
be :
Organic small
molecule.
Complementary in
shape to the
target.
Oppositively
charge to the

Structure based drug

design
Structure-based drug design
relies on knowledge of the
three dimensional structure
of the biological target
obtained through methods
such as
x-ray crystallography

Target selection

There are potentially many ways in

which biochemical pathways could
become abnormal and result in disease.
Therefore, knowledge of the molecular
basis of the disease is important in
order to select a target at which to
disrupt the process.
Target selection Categories :
Target for mechanistic drug design
usually fall into three:
enzymes,
receptors

Structure
Determination
(Crystal Structure of Target
Protein
Can be taken from PDB
database)

Protein Data bank (PDB)

The repository reservoir data bank to store

the authenticated structures of "protein and
nucleic acid" Single worldwide database and
hundreds of secondary database categorize
the data differently.
Key resource in the area of structural
biology, stores 3D structural Data of large
biological molecules such as protein and
nucleic acid
Data is submitted by biologists and
biochemists from all around the world to be
freely accessible on internet via Its member
organization website and is updated weekly.

Supported and Funded

The protein data bank (PDB) is operated by :
Rutgers, The State University of New Jersey.
The San Diego Supercomputer Center at the
University of California, San Diego.
The Center for Advanced Research in
Biotechnology of the National Institute of
Standards and Technology the Research
Collaboratory for Structural Bioinformatics
(RCSB)
The PDB is supported by funds from the
National
Science
Foundation,
the
Department of Energy, and the National
Institutes of health.

Determination of active site

of
target protein
Only a small part of a lead
compounds may be involved in
the appropriate interaction. The
relevant groups on a molecule
that interact with the receptor
and are responsible for activity
are
collectively
known
as

Molecular docking
Docking is a method which
predicts
the
preferred
orientation of one molecule to a
second when bound to each
other to form a stable complex.

Retrieving 3D Structures :

What is VMD?

VMD (Visual Molecular Dynamics) is a molecular

visualization program for displaying, animating, and
analyzing large biomolecular systems such as
proteins, nucleic acids, lipid bilayer assemblies, etc.
using 3-D graphics and built-in scripting.
VMD supports computers running MacOS X, Unix, or
Windows, is distributed free of charge, and includes
source code. It may be used to view more general
molecules, as VMD can read standard Protein Data
Bank (PDB) files and display the contained structure.
VMD provides a wide variety of methods for rendering
and coloring a molecule. VMD can be used to animate
and analyze the trajectory of a molecular dynamics
(MD) simulation.
In particular, VMD can act as a graphical front end for
an external MD program by displaying and animating
a molecule undergoing simulation on
a remote

Key Features of VMD

General 3-D molecular visualization with extensive
drawing and coloring methods
Extensive atom selection syntax for choosing
subsets of atoms for display
Visualization of dynamic molecular data
Visualization of volumetric data
Supports all major molecular data file formats
No limits on the number of molecules or trajectory
frames, except available memory
Molecular analysis commands
Rendering
high-resolution,
publication-quality
molecule images
Movie making capability
Building and preparing systems for molecular
dynamics simulations
Interactive molecular dynamics simulations
Extensions to the Tcl/Python scripting languages

BENEFITS OF
COMPUTER
AIDED DRUG
DESIGN

DRUGS DISCOVERY :

Elimination of compounds
with undesirable
properties
Design of in silico filters to
eliminate compounds with
undesirable properties (poor
activity
and/or
poor
Absorption
Distribution,
Metabolism,
Excretion
and
Toxicity,

Thank You