drug formulation made easy

1. Topic : Computer Aided Drug Design (CADD)
BY- Dr Zaid Wani

2. INTRODUCTION
• Drug design which relies on computer modeling
techniques is referred to as computer-aided drug
design.
• Computer-aided drug design uses computational
chemistry to discover, enhance, or study drugs
and related biologically active molecules.
• The most fundamental goal is to predict whether
a given molecule will bind to a target and if so
how strongly.
• Overcome the limitations of conventional
methods.

5. • CADD can be done in two ways : Ligand based
or receptor based.
• Ligand based design uses a known set of
ligands, but an unknown receptor site.
• Receptor-based drug design (or direct drug
design) relies on knowledge of the three
dimensional structure of the biological target.
• Both approaches are actually very similar.

6. Ligand Based Drug Design
• It uses a known set of ligands, but an unknown receptor site.
• These other molecules may be used to derive a pharmacophore
model that defines the minimum necessary structural
characteristics a molecule must possess in order to bind to the
target.
• In other words, a model of the biological target may be built based
on the knowledge of what binds to it, and this model in turn may be
used to design new molecular entities that interact with the target.
• Alternatively, a Quantitative Structure – Activity Relationship
(QSAR), in which a correlation between calculated properties of
molecules and their experimentally determined biological activity ,
may be derived . These QSAR relationship in turn may be used to
predict the activity of new analogs.

7. Receptor Based Drug Design
• Structure- based drug design (or direct drug design )
relies on knowledge of the three dimensional structure
of the biological target obtained through methods such
as X-ray crystallography or NMR spectroscopy.
• If an experiment structure of a target is not available, it
may be possible to create a homology model of the
target based on the experimental structures of the
related protein.
• Using the structure of the biological target, candidate
drugs that are predicted to bind with high affinity and
selective to the target may be designed using
interactive graphics and the intuition of a medical
chemist.

8. • The first phase is to determine the three
dimensional structure of the protein (receptor)
either by X-ray or NMR and identify the binding
site (drug target ) using standard structural
analysis from X-ray diffraction, NMR.
• In the absence of the structural information,
homology of the unknown receptor sequence
with known structures that have been identified
through database searches may be good starting
point.

9. • The second phase is to generate a query for
database searching.
• This model may be based on a pharmacophore
(functional group types eg, H-bond donor,
acceptors, hydrophobic regions and the spatial
arrangement of those groups on a molecule that
interact with the receptor and are responsible for
binding and biological activity)
• The query is generated by building a simplified
model of the receptor site.

10. • The third phase is to search database for
ligands that may bind to the Chosen receptor.
• The 3D pharmacophore is used in
conformationally flexible searches for ligands
that match the spatial distribution of receptor.

11. • Docking can be accomplished by either
geometric matching of the ligand and its
receptor or by minimizing the energy of
interaction.

12. ADME
• The deposition of a pharmaceutical
compound may be described by its
pharmacokinetic or ADME properties.
• In order to exert pharmacological effect in
tissues , a compound has to penetrate various
physiological barriers , such as GIT barrier,
BBB, and the microcirculatory barrier , to
reach the blood circulation.

13. • It is subsequently transported to its effector
site for distribution into tissues and organs ,
degraded by specialized enzymes, and finally
removed from the body via excretion.
• Genetic variation in drug metabolizing
enzymes implies that some compounds may
undergo metabolic activation.
• Excretion.

14. • Clinical trials
• FDA appoval
• Drug is ready to use

15. THANKYOU