Simulation of multiphase systems utilizing independent force fields to control intraphase and interphase behavior

Abstract

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.

Modeling and simulation of protein–surface interactions: achievements and challenges

“…The authors compared experimental findings with their computed free energies of adsorption and qualitative behavior of peptides on different SAM surfaces such as the change in conformation upon adsorption and the orientation on the surface. This study (Collier et al 2012) demonstrated that although some FFs perform reasonably well (the best match to experiment was obtained in simulations using CHARMM22 and AMBER94 (Cornell et al 1995)), none of the FFs capture the specific interaction properties of the SAM-water interface. In particular, systematic overestimation of the binding strength of hydrophobic peptides and underestimation for negatively charged peptides was observed.…”

“…In the last decade, however, much effort has been invested to evaluate and adapt biomolecular FFs to the simulation of interfaces between biomolecules in water and specific inorganic materials, and several new approaches for developing general bio-inorganic FFs have been reported. For example, a dual-scale FF that includes two sets of partial atomic charges, optimized for each phase separately, has been developed (Biswas et al 2012). In the recently reported INTERFACE FF , partial atomic charges and van der Waals parameters have been optimized using a non-polarizable fixed-charge model for a large number of different materials based on the properties of the solid surfaces, e. g. crystal unit parameters, surface tension, water contact angle and interfacial tension, and adsorption energy of selected peptides.…”

“…The Dual-FF (Biswas et al 2012), (discussed in more detail in Sec.7·5) was optimized to reproduce the experimental binding energies of TGTG-X-GTGT peptides, with X = N, D, G, K, F,T, W and V, on hydroxylated quartz (100) and glass surfaces in MD simulations (Snyder et al 2012). In the Dual-FF, CHARMM parameters were used for biomolecules, while interfacial parameters, such as partial charges and Lennard-Jones parameters for silica-peptide and silica-water interactions, were tuned to obtain the best agreement with peptide adsorption energies.…”

“…The applicability of several commonly used biomolecular FFs for the simulation of peptide adsorption on hydrophobic and hydrophilic SAMs has been systematically evaluated by Latour and colleagues for CHARMM19 (Sun & Latour, 2006;Sun et al 2007;Vellore et al 2010), and CHARMM22, OPLS-AA, and AMBER94 (Collier et al 2012) FFs. In the latter study by Collier et al (2012), the FF parameters and partial charges of the SAMs (-OH and -COOH) were assigned by analogy to amino acids with similar functional groups.…”

“…In the latter study by Collier et al (2012), the FF parameters and partial charges of the SAMs (-OH and -COOH) were assigned by analogy to amino acids with similar functional groups. The authors compared experimental findings with their computed free energies of adsorption and qualitative behavior of peptides on different SAM surfaces such as the change in conformation upon adsorption and the orientation on the surface.…”