A fundamental molecular-level understanding of protein-surface interactions (PSIs) is crucial for many applications in chemistry, biomaterials design in biomedical engineering, and biodefense. All-atom empirical force field molecular dynamics (MD) simulation methods hold great promise as a valuable tool for understanding and predicting PSIs. However, current MD force fields have not been verified for this application. In this study interfacial force field (IFF) parameters for use with the CHARMM force field have been developed for the accurate MD simulation of peptide adsorption on high-density polyethylene (HDPE). Parameterization of the IFF was performed to achieve agreement between calculated adsorption free energies (∆G°ads) of small TGTG-X-GTGT host-guest peptides (T = threonine, G = glycine, and X = variable amino-acid residue picked from different characteristic types) on HDPE with the experimental values within ±1.0 kcal/mol. This IFF parameter set consists of tuned nonbonded parameters (i.e., partial charges and Lennard-Jones parameters) for use with an in-house-developed modified CHARMM MD program that enables the use of an independent set of force field parameters to control molecular behavior at a solid-liquid interface. The value of R2 in the correlation between the simulation and experimental peptide adsorption results increased from 0.0, when standard CHARMM force field parameters were used, to 0.8, for the tuned IFF parameters. Subsequent studies are currently under way in which the tuned IFF parameter set is applied for the simulation of protein adsorption behavior on HDPE surface.

Interfacial force field parameterization in CHARMM for the accurate representation of peptide adsorption free energy on high-density polyethylene

249th National Meeting (2015)

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