Paper BI+MG-WeA3
Interfacial Force Field Parameterization in CHARMM for the Accurate Molecular Dynamics Simulation of Peptide Adsorption on High-Density Polyethylene

Wednesday, November 12, 2014, 3:00 pm, Room 317

A fundamental molecular-level understanding of protein-surface interactions (PSIs) is crucial for many applications in biotechnology and bioengineering. All-atom molecular dynamic (MD) simulation methods hold great promise as a valuable tool for understanding and predicting PSIs. However, current MD force fields have not been validated for this application. In this study, adsorption free energy (∆G_ads) of small TGTG-X-GTGT host-guest peptides (T = threonine, G = glycine, and X = variable amino acid residue) on a high-density polyethylene (HDPE) surface (110 crystalline plane) using the CHARMM force-field were calculated and compared with experimental results in order to find inaccuracies. In order to accurately calculate ∆G_ads in our simulation studies, advanced sampling methods such as umbrella sampling and replica-exchange MD were used to provide adequate conformational sampling of the peptides over the HDPE surface. Results revealed substantial discrepancies between the simulation and the experimental ∆G_ads values (i.e., differences exceeding 1.0 kcal/mol). To correct the adsorption behavior, an in-house-developed interfacial force-field (IFF) was incorporated into the simulation program with IFF parameters adjusted until satisfactory agreement with the experimental data set was achieved. Subsequent studies are planned to apply the tuned IFF to simulate the adsorption behavior of lysozyme and ribonuclease A proteins to HDPE, for which synergistically matched experimental studies have also been conducted to validate the developed method for protein-adsorption simulations.