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Computer Aided Drug Designing


Drug design is the approach of discovery a new drug by design, based on
their biological targets. Typically a drug target is a key molecule involved
in a particular metabolic or signaling pathway that is specific to a
disease and disorders.

The Rational Drug Designing is unlike the historical method of drug
discovery, by trial-and-error testing of chemical substances on animals,
and matching the apparent effects to treatments, rational drug design
begins with knowledge of specific chemical responses in the body or
target organism, and tailoring combinations of these to fit a treatment
profile. Since the computers are used to designing the drug virtual it is
called Computer Aided Drug Designing (CADD).

There are different approaches of drug designing,
Structure Based Drug Designing
Analog Based Drug Designing
Fragment Based Drug Designing

Structure Based Drug Designing
In structure-based drug design, the three-dimensional structure of a
drug target interacting with small molecules is used to guide drug
discovery. "Structure-based drug design represents the idea that you can
see exactly how your molecule interacts with its target protein".

Analog Based Drug Designing
In many instances where the 3D structure of the binding site is
unknown, analog based drug designing approach is used. This can be
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achieved by pharmacophore modeling and developing 3D interaction map
based on known active analogs for the intended target.

Fragment Based Drug Designing
Fragment-based drug design is a new approach that has been
successfully applied to challenging targets, such as protein-protein
interactions. While 3-D protein structures have been used in drug
discovery for many years now, fragment-based drug design uses x-ray
crystallography or other physical techniques to screen fragment libraries
for specific binding to a target protein. Knowledge of exactly how the
fragments bind to the protein target allows the hits to be optimized by
growing the fragments or by combining and linking different fragments.

In in-silico method that utilizes chemical feature-based pharmacophores
in a fragment-based approach both for the design of novel compounds,
and for lead optimization. Starting with small fragment units with known
binding interactions, chemical lead series can be rapidly discovered and
optimized for drug-like properties. Advantages of starting from
fragments include an increased diversity in chemical space, but also the
flexibility to incorporate drug-like properties at early stages of the
design.









SUSHIL KUMAR, DEPT. of APPLIED GENETICS

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