Computer Simulations of Enzyme Reaction Mechanisms: Application of a Hybrid Genetic Algorithm for the Superimposition of Three-Dimensional Chemical Structures

Enzymes play a key role in research of the pharmaceutical industry because they represent targets for the design of new drugs. Therefore, the determination of the mode of action of enzymes is one of the great challenges of modern chemistry and an important task in

rational drug design

. The situation is aggravated by the fact that the number of enzymes with known three-dimensional structure is small compared to the number of pharmaceutically relevant enzymes. Therefore, approaches for searching for a new

lead structure

depend on the information available about the protein structure and the ligands binding to a particular target. In this article we present a methodology based on a ligand-based approach. It can also be employed if the three-dimensional structure of the target of interest is not known. The structures of a set of molecules are superimposed based on a

parallel implementation

of a

genetic algorithm

(GA) to evaluate their

maximum common three-dimensional substructure

. This is an important step in the identification of a

pharmacophoric pattern

for molecules that bind to the same receptor. With this method it is possible to determine a complementary map of the receptor binding pocket.