Molecular dynamics simulations and theory of intermolecular interactions in solutions

Abstract

In the study of biological systems, molecular dynamics (MD) simulations have played an important role in providing atomic details for phenomena of interest. The force field used in MD simulations is a critical factor determining the quality of the simulations. Recently, Kirkwood-Buff (KB) theory has been applied to study preferential interactions and to develop a new force field. KB theory provides a path from quantities determined from simulation data to the corresponding thermodynamic data. Here we combine KB theory and molecular simulations to study a variety of intermolecular interactions in solution. First, recent results concerning the formulation and evaluation of preferential interactions in biological systems in terms of KB integrals are presented. In particular, experimental and simulated preferential interactions of a cosolvent with a biomolecule in the presence of water are described. Second, a force field for the computer simulation of aqueous solutions of amides is presented. The force field is designed to reproduce the experimentally observed density and KB integrals for N-methylacetamide (NMA), allowing for an accurate description of the NMA activity. Other properties such as the translational diffusion constant and heat of mixing are also well reproduced. The force field is then extended to include N,N'-dimethylacetamide and acetamide with good success. The models presented here provide a basis for an accurate force field for peptides and proteins. Comparison between the developed KB force fields (KBFF) and existing force fields is performed for amide and glycine and proves that the KBFF approach is competitive. Also, explicit expressions are developed for the chemical potential derivatives, partial molar volumes, and isothermal compressibility of solution mixtures involving four components at finite concentrations using the KB theory of solutions. A general recursion relationship is also provided which can be used to generate the chemical potential derivatives for higher component solutions. Finally, a pairwise preferential interaction model (PPIM), described by KB integrals is developed to quantify and characterize the interactions between functional groups observed in peptides.