A Statistical Mechanics Theory of Molecular Recognition

Abstract

A novel theoretical approach to the molecular recognition process in protein is presented, based on the statistical mechanics of molecular liquids, or the reference interaction site model/three-dimensional reference interaction site model (RISM/3D-RISM) theory. The method requires just the structure of protein and the potential energy parameters for the biomolecule and solutions as inputs. The calculation is carried out in two steps. The first step is to obtain the pair correlation function for solutions consisting of water and ligands based on the RISM theory. Then, given the pair correlation functions prepared in the first step, we calculate the 3D-distribution functions of water and ligands around and inside protein based on the 3D-RISM theory. The molecular recognition of a ligand by the protein is realized by the 3D-distribution functions: if one finds some conspicuous peaks in the distribution of a ligand inside the protein, then the ligand is regarded as “recognized” by the protein. Some molecular recognition processes of small ligands, including water, noble gases, and ions, by a protein are presented in this chapter. The relation of the molecular recognition process to the pressure denaturation of protein is also discussed.