Appendix 2: Morphometric Approach

Abstract

The hydration of a biomolecule with a fixed structure can be decomposed into the following two processes: process 1, the hydrophobic hydration, where a cavity matching the polyatomic structure of the biomolecule is created; and process 2 where biomolecule-water van der Waals and electrostatic interaction potentials are taken into account. In process 1, the cavity is treated as a solute in the angle-dependent integral equation (ADIE) theory, the most reliable statistical-mechanical theory for solute hydration. However, such a complexly shaped solute cannot directly be handled by the ADIE theory because of the mathematical complications encountered. We have solved this problem by combining the ADIE theory with the morphometric approach (MA). In this chapter, we briefly summarize the basic characteristics of the MA. Our new hybrid method where this ADIE-MA theory and the three-dimensional reference interaction site model (3D-RISM) theory are applied to processes 1 and 2, respectively, is capable of calculating the hydration free energy, energy, and entropy of a large polyatomic solute like a protein with sufficient accuracy and high speed.