Section: Application Domains

Pharmaceutics and Drug Design

Drug design is the inventive process of finding new medications based on the knowledge of the biological target. The drug is most commonly an organic small molecule which activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves design of small molecules that are complementary in shape and charge to the biomolecular target to which they interact and therefore will bind to it. Drug design frequently relies on computer modeling techniques. This type of modeling is often referred to as computer-aided drug design.

Structure-based drug design attempts to use the structure of proteins as a basis for designing new ligands by applying accepted principles of molecular recognition. The basic assumption underlying structure-based drug design is that a good ligand molecule should bind tightly to its target. Thus, one of the most important principles for designing or obtaining potential new ligands is to predict the binding affinity of a certain ligand to its target and use it as a criterion for selection.

We develop new methods to estimate the binding affinity using an approximation to the binding free energy. This approximation is assumed to depend on various structural characteristics of a representative set of native complexes with their structure solved to a high resolution. We study and verify different structural characteristics, such as radial distribution functions, and their affect on the binding free energy approximation.