Detail about in silico drug design and virtual screening technique

1. IN-SILICO DRUG DESIGN AND VIRTUAL
SCREENING TECHNIQUE
PERSENTED TO
Dr. ARUN KUMAR
Faculty of pharmacy
Integral university
PRESENTED BY:-
SHAFIURRAHMAN
SAUD AHMAD
M.Pharm ist year ,2 sem

2.  Drug Design : Based on the knowledge of the biological target, finding a
new medication is what we called as drug design.
 In Silico drug design: Drug design when performed in computers using
computational software is known as in silico drug design.
 Since the electronic chips used in the computers are usually made up of
silicon, hence came the name in silico drug design.
 In silico is also an expression used to mean ‘performed on computer or via
computer simulation.

3. Types of In silico Drug Design :
I. Ligand Based Drug Design
II. Structure Based Drug Design

4. LIGAND BASED DRUG DESIGN
 Ligand: It is simply a molecule that binds to target. Often a soluble molecule
such as hormone or neurotransmitter that binds to a receptor.
 In this type of drug design,the receptor is unknown but the ligand is known.
 It is also the statistical analysis of what groups are important for biological
activity.
 LBDD relies on the knowledge of other molecules that bind to the biological
target of interest.
 Used to derive a pharmacophore.
 Also defines the minimum necessary structural characteristics a molecule must
possess in order to bind to the target.

6. STRUCTURE BASED DRUG DESIGN
 In case of SBDD its just opposite of LBDD,where the receptor is
known whereas the ligand is unknown.
 Completely relies on the knowledge of the 3D structure of the
biological target.
 Methods by which the 3D structure of biological target are
obtained are mentioned below.
I. X-ray crystallography
II. NMR spectroscopy
III. Homology modelling

7. VIRTUAL SCREENING TECHNIQUES
 Virtual screening is a computational technique used in drug discovery to
search the libraries of small molecules in order to identify those
structures which are most likely to bind to a drug target, typically a
protein receptor or enzyme.
 It is also defined as a ‘automatically evaluating very large libraries of
compounds 'using computer programs.

8. CATEGORIES OF SCREENING
There are two broad categories of screening techniques:
I. Ligand based screening
II. Structure based screening

9. LIGAND-BASED VIRTUAL SCREENING
 A model of the ligand can be built by exploiting the collective
information contained in such set of ligands. These are known as
pharmacophore models.
 A candidate ligand can there be compared to the pharmacophore
model to determine whether it is compatible with it and therefore
likely to bind.
 Another approach to LB virtual screening is to use 2D chemical
similarity analysis method to scan a database of molecules against
one or more active ligand structure.

10.  A popular approach to LBVS is based on searching molecules with shape
similar to that of known actives, as such molecules will fit the targets binding
site and hence will be likely to bind the target.
 One of the important type of LBVS is- .Similarity based virtual screening:The
similar property principle states that structurally similar molecules tends to
have similar properties.
 A active reference structure is provided and a database of compounds are
ranked in an order based on similarity to the reference.
 Select the top ranking compound for biological testing.
 But similarity is inherently subjective,so need to provide a quantitative basis,a
similarity measure,for ranking structures.

11. STRUCTURAL BASED VIRTUAL SCREENING
 Structural based virtual screening begins with the identification of a
potential ligand-binding site on the target molecule.
 Ideally the target site is a pocket or protuberance having a variety of
probable hydrogen bond donors and acceptors, hydrophobic characteristics,
and with molecular adherence surfaces.
 The ligand-binding site can be the active site as in an enzyme; an assembly
site with another macromolecule or a communication site, which is
necessary in the mechanism of the molecule.

12.  Determining the structure of a target protein by NMR, X-ray crystallography or
homology modelling befalls as a major and initializing stair in structure based
virtual screening.
 Numerous X-ray crystallographic and NMR studies are helpful in determining
the Virtual Screening perimental structures of ligands bound to the enzymes,
serve as a major source of ideas for analogue design, intern useful for the
docking studies.

13. REFEENCES
I. Wikipedia
II. Slide share

14. Thank
you