Abstract

MOLECULAR DESIGN OF DRUG ON REVIEW

E. Ajila*, R. Aniz K. Roy, Sheeja Reka A. G., Prasobh G. R., M. S. Padmaja Devi, Dhanya S. and Athira A. S.

ABSTRACT

Molecular design is the application of all techniques leading to the discovery of new chemical entities with specific properties required for the intended application. Computational molecular design is a useful tool in modern drug discovery. Virtual screening is an approach that evaluates individual members of compound libraries. In contrast, design approaches construct compounds by combining scaffolds and side groups to optimize the calculated binding affinity. Pharmaceutical research has successfully incorporated a wealth of molecular modeling method, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Flexibility of target binding site is an essential but frequently overlooked aspect to be considered in molecular docking. Enzymes and receptors can undergo conformational changes during the molecular recognition process. In some cases these structural rearrangements are small and the ligand fits in a binding site with little mobility. Otherwise, some proteins undertake significant conformational changes, which can involve elements of secondary and tertiary structure. Such flexibility issues can be handled by the use of techniques such as MD. Molecular dynamics applies Newton’s equations of motion, as described in classical mechanics, to specify the position and speed of each atom in the system under study.

Keywords: Molecular Modeling, Software.