Molecular Recognition and Binding Free Energy Calculations in Drug Development

B.   N.   Dominy

Abstract

The functional capabilities of biological systems, such as enzyme catalysis, nutrient import, and cell signaling, depend crucially on specific molecular interactions. In addition, the effects of common drugs also act through a mechanism of binding to specific biomolecular targets. Models for the prediction of binding affinity are used in basic research to study the molecular basis of biological function as well as in applied research to study the development of new drugs. This review will address the biological importance of molecular recognition as well as its influence on the development of pharmaceuticals. Further, a broad overview of computational approaches used for the prediction of biological activity and specifically binding free energy will be presented.

Keywords: Computational, free energy, binding affinity, thermodynamics, enhanced sampling, QSAR, ADME, Knowledge-Based potentials, drug design, empirical scoring functions