Selected Microscopic and Mezoscopic Modelling Tools and Models – an Overview

Abstract

In order to model (bio)molecular systems and to simulate their dynamics one requires the potential energy functions at the microscopic, classical and/or quantum levels, as well as fast generators of the free-energy functions at the mezoscopic level. A brief overview of the methods which allow computations of the potential energy functions and the free energies is presented. The ongoing research is focused on designing molecular mezoscopic interaction potentials, applicable to nanoscale (bio)molecular systems, and on utilizing conformationally dependent atomic charges. In particular, the coupling of a fast quantum SCC-DFTB method with the Poisson-Boltzmann (PB) or Generalized Born (GB) models is discussed, and the role of the SCC-DFTB CM3 charges in computations of the mean-field electrostatic energies of molecular systems in real molecular environments is indicated. These charges reproduce very well molecular dipole moments, and are obtained from the Mülliken ones by applying a mapping procedure, using a quadratic function of the Mayer’s bond orders. The PB and GB models give electrostatic reaction field energies of molecular environments, in particular, provide electrostatic contributions to the salvation energies. It is assumed that the solvation energy consists of the mean-field electrostatic and nonpolar (hydrophobic) energy contributions. Typically, the nonpolar term consists of the cavity formation free energy, and sometimes also of a mean van der Waals interaction energy of the molecular system with its environment. This allows to reproduce experimental solvation/hydration energies assuming different analytical forms of the nonpolar energy terms. Refined GB models, with new formulae for the Born radii are discussed. The nonpolar energies are quite well reproduced using the solvent accessible surface area (SASA), or a polynomial series depending on reciprocal values of the Born radii. Presence of the mean van der Waals energy on the quality of the fits is also discussed. Reliable mezoscopic models and theories play a key role in describing the functioning of nanoscale (bio)molecular systems