Parameterization of an interfacial force field for accurate representation of peptide adsorption free energy on high-density polyethylene.

Interfacial force field (IFF) parameters for use with the CHARMM force field have been developed for interactions between peptides and high-density polyethylene (HDPE). Parameterization of the IFF was performed to achieve agreement between experimental and calculated adsorption free energies of small TGTG-X-GTGT host-guest peptides (T = threonine, G = glycine, and X = variable amino-acid residue) on HDPE, with ±0.5 kcal/mol agreement.

Development of a tuned interfacial force field parameter set for the simulation of protein adsorption to silica glass.

Adsorption free energies for eight host-guest peptides (TGTG-X-GTGT, with X = N, D, G, K, F, T, W, and V) on two different silica surfaces [quartz (100) and silica glass] were calculated using umbrella sampling and replica exchange molecular dynamics and compared with experimental values determined by atomic force microscopy. Using the CHARMM force field, adsorption free energies were found to be overestimated (i.e.

Comparison between empirical protein force fields for the simulation of the adsorption behavior of structured LK peptides on functionalized surfaces.

All-atom empirical molecular mechanics protein force fields, which have been developed to represent the energetics of peptide folding behavior in aqueous solution, have not been parameterized for protein interactions with solid material surfaces. As a result, their applicability for representing the adsorption behavior of proteins with functionalized material surfaces should not be assumed. To address this issue, we conducted replica-exchange molecular dynamics simulations of the adsorption behavior of structured peptides to functionalized surfaces using three protein force fields that are widely used for the simulation of peptide adsorption behavior: CHARMM22, AMBER94, and OPLS-AA.

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

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. Whereas 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.

Development of molecular simulation methods to accurately represent protein-surface interactions: The effect of pressure and its determination for a system with constrained atoms.

When performing molecular dynamics simulations for a system with constrained (fixed) atoms, traditional isobaric algorithms (e.g., NPT simulation) often cannot be used.

Assessment of the transferability of a protein force field for the simulation of peptide-surface interactions.

In order to evaluate the transferability of existing empirical force fields for all-atom molecular simulations of protein adsorption behavior, we have developed and applied a method to calculate the adsorption free energy (DeltaG(ads)) of model peptides on functionalized surfaces for comparison with available experimental data. Simulations were conducted using the CHARMM program and force field using a host-guest peptide with the sequence TGTG-X-GTGT (where G and T are glycine and threonine amino acid residues, respectively, with X representing valine, threonine, aspartic acid, phenylalanine or lysine) over nine different functionalized alkanethiol self-assembled monolayer (SAM) surfaces with explicitly represented solvent. DeltaG(ads) was calculated using biased-energy replica exchange molecular dynamics to adequately sample the conformational states of the system.