Nanotech 2010 Vol. 3
Nanotech 2010 Vol. 3
Nanotechnology 2010: Bio Sensors, Instruments, Medical, Environment and Energy

Nano Medical Sciences Chapter 7

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

Authors: A. Kovalenko

Affilation: National Institute for Nanotechnology, Canada

Pages: 440 - 443

Keywords: molecular theory of solvation, molecular dynamics, AMBER package, computer-aided drug design, binding affinity, chaperonin, prion proteins

We have coupled the statistical-mechanical, molecular theory of solvation (a.k.a. 3D-RISM-KH) with molecular dynamics (MD) simulation in the Amber molecular dynamics package to contract solvent degrees of freedom. This included a number of accelerating schemes with several cutoffs for the interaction potentials and correlation functions, an iterative guess for the 3D-RISM solutions, and extrapolating solvent-induced forces and applying them in large multi-time steps (up to 20 fs) to enable simulation of large biomolecules. The coupled MD/3D-RISM-KH method makes feasible modeling of biomolecular structures of practical interest and thus has tremendous potential for computer-aided drug design. It allows one to study processes on extremely long timescales, as the solvent dynamics is accounted for statistically-mechanically. It replaces the MM/GBSA or MM/PBSA post-processing suffering from the empirical treatment of non-polar contributions with the MM/3D-RISM-KH accurate evaluation of the solvation thermodynamics. It yields 3D maps of binding affinity at once without any phenomenological approximations. This presentation will introduce the new MD/3D-RISM-KH method and will show how it yields function-related properties for biomolecular systems as large and complex as a solvated chaperonin (GroEL) and predicts binding maps of prion proteins for development of novel inhibitors of prion protein conversion.

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

ISBN: 978-1-4398-3415-2
Pages: 880
Hardcopy: $189.95