Simulation of Multiphase Systems Utilizing Independent Force Fields to Control Intra-Phase and Inter-Phase Behavior

摘要

Fixed-charge empirical force fields have been developed and widely used over the past three decades for all-atom molecular simulations. Most simulation programs providing these methods enable only one set of force field parameters to be used for the entire system. While this is generally suitable for single-phase systems, the molecular environment at the interface between two phases may be sufficiently different from the individual phases to require a different set of parameters to be used to accurately represent the system. Recently published simulations of peptide adsorption to material surfaces using the CHARMM force field have clearly demonstrated this issue by revealing that calculated values of adsorption free energy substantially differ from experimental results. While nonbonded parameters could be adjusted to correct this problem, this cannot be done without also altering the conformational behavior of the peptide in solution, for which CHARMM has been carefully tuned. We have developed a dual-force-field approach (Dual-FF) to address this problem and implemented it in the CHARMM simulation package. This Dual-FF method provides the capability to use two separate sets of nonbonded force field parameters within the same simulation: one set to represent intra-phase interactions and a separate set to represent inter-phase interactions. Using this approach, we show that interfacial parameters can be adjusted to correct errors in peptide adsorption free energy without altering peptide conformational behavior in solution. This program thus provides the capability to enable both intra-phase and inter-phase molecular behavior to be accurately and efficiently modeled in the same simulation.