Calculation Of The Free Energy Of Peptide-surface Interactions By Molecular Dynamics Simulation

摘要

Although it is well recognized that the bioactivity of proteins adsorbed on biomaterial surfaces mediates cellular response, very little is understood about the specific molecular mechanisms involved. Once properly developed, empirical force field-based.molecular simulation methods should serve as a valuable resource to help elucidate the mechanisms governing protein adsorption behavior. Our laboratory has been working on the development of molecular dynamics (MD) methods for this application for the past several years.~(1-3) Recently we have used MD simulations to model peptide-surface interactions with a potential of mean force (PMF) method applied to calculate adsorption free energy (ΔA) as a function of peptide-surface separation distance (SSD) 3 for comparison to experimental results.~4 From these studies, we have realized that simulations tend to become 'stuck' in low-energy conformations and that biased sampling methods, such as umbrella sampling,~(5-7) are needed to enable a sufficient SSD range to be sampled for the proper calculation of ΔA. The objective of this research was therefore to develop and demonstrate the use of a biased sampling method to enable ΔA between two interacting molecular species to be determined as a function of SSD by MD simulation using CHARMM, and to compare the simulation results to the same system without biased sampling and to the exact analytical solution for the molecular system simulated.