To improve the lead compound, chemists can do rational drug design. They
can systematically alter the structure of the lead compound to provide different
compounds that are more effective and have fewer side effects. The structures of
compounds drawn in silico can be docked to the target proteins and interaction energies
calculated. Databases of biochemical and medicinal interactions can be evaluated using
network theory to find new targets for therapy. Computer programs can be used to
calculate molecular and quantum mechanical descriptors, which can be correlated to the
measured properties in a quantitative structure-activity relationship, or QSAR. Other
tools of rational drug design are to model molecular structures and their binding to
potential targets, do combinatorial synthesis and high throughput screening for any of a
number of biological effects. One can also look for the genetic cause of a disease and a
way to deliver the correct gene into the patient in gene therapy.
Keywords: Rational drug design, QSAR, combinatorial synthesis, high
throughput screening.