QM/MM approaches in medicinal chemistry research.

ABSTRACT

One of the goals of medicinal chemistry concerns the ability to compute protein-ligand interactions based on the structural knowledge of the receptor. To this end, the majority of current approaches incorporate classical force field potentials to describe receptor-ligand interactions. One of the most critical problems of standard molecular mechanics (MM) force fields is their fixed-charge treatment of electrostatic interactions. Two problems are derived from this approximation, polarization and charge transfer. As an immediate step in computational complexity, it seems natural to incorporate Quantum Mechanics (QM) within a hybrid QM/MM approach, which has shown to be a useful tool to describe structural and mechanistic aspects of chromophores and prosthetic residues in proteins. In this review, we describe specifically the role of QM/MM methods and their various applications to computational drug design and medicinal chemistry research in general.