1 - The Molecular Modeling Perspective in Drug Design

Abstract

Molecular modeling has become a new discipline in pharmaceutical research that has grown very rapidly and has contributed to the discovery of new lead compounds. The evolution of this discipline is progressively unfolding, leading to a new era of intelligent approaches in drug design. The concepts used in 3D drug design are quite simple. New molecules are conceived either on the basis of similarities with known reference structures or on the basis of their complementarity with the 3D structure of known active sites. Molecular interactions are regulated by subtle recognition and discrimination processes whereby the 3D features and the binding energies play an important role. Molecular modeling is a discipline that contributes to the understanding of these processes in a qualitative and sometimes quantitative way. It not only presents means for analyzing the details of the molecular machinery involved in a known system and understanding the way the biological system functions, but it also provides the necessary tools for predicting the potential possibilities of prototype candidate molecules. Molecular modeling can be simply considered as a range of computerized techniques based on theoretical chemistry methods and experimental data that can be used either to analyze molecules and molecular systems or to predict molecular and biological properties. The techniques currently available provide extensive insight into the precise molecular features that are responsible for the regulation of biological processes: molecular geometries, atomic and molecular electronic aspects, and hydrophobic forces. All these structural characteristics are of primary importance in the understanding of structure-activity relationships and in rational drug design.