Multiscale methods for nanochemistry and biophysics in solution

Statistical-mechanical, 3D-RISM-KH molecular theory of solvation is an integral equation theory of molecular liquids capable of describing, from the first principles, solvation structure and thermodynamics in complex nanoscale systems. The 3D-RISM-KH theory accurately yields the solvation structure for biomolecular systems as large as chaperonins and ion channels. It predicts 3D maps of ligand binding affinity at once without using empirical scoring functions, and has significant potential for computer-aided drug design. Recently, the 3D-RISM-KH theory was coupled with MD simulations by contracting solvent degrees of freedom to treat solvated biomolecules, and the MD/3D-RISM-KH multiscale method was implemented in the Amber molecular dynamics package [T. Luchko et al., 2010, [29]]. The MD/3D-RISM-KH method allows one to study biomolecular processes on extremely long timescales, as the statistics of rare solvent and ligand events is accounted for analytically. We further replaced the MM/GB(PB)SA post-processing which evaluates the free energy by empirical treatment of non-polar solvation effects with the MM/3D-RISM-KH method which employs 3D-RISM-KH to evaluate the solvation thermodynamics. In this paper, we briefly review the 3D-RISM-KH theory as well as the MD/3D-RISM-KH multiscale method implemented in the Amber package. We illustrate the MM/3D-RISM-KH method on binding of thiamine (vitamin of group B) to extracytoplasmic thiamine-binding lipoprotein MG289, and on the microscopic solvation properties of the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel (GLIC) homologue. © 2011 Published by Elsevier B.V. All rights reserved.