3D Molecular Theory of Solvation Coupled with MD for Nanomedical Sciences

We coupled statistical-mechanical, molecular theory of solvation (a.k.a. 3D-RISM-KH) contracting solvent degrees of freedom with MD simulation in the Amber package. This included a number of accelerating schemes with cutoffs and iterative guess for the correlation functions, and extrapolating solvent-induced forces and applying them in large multi-time steps (up to 20 fs) to enable simulation of large biomolecules. 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. It replaces MM/GB(PB)SA post-processing using empirical treatment of non-polar contributions with MM/3D-RISM-KH evaluation of the solvation thermodynamics. The method accurately yields the solvation structure for biomolecular systems as large as a chaperon (GroEL) and 3D maps of ligand binding affinity at once without phenomenological approximations, and has significant potential for computer-aided drug design.