Interfacial Force Field Parameterization in CHARMM for the Accurate Molecular Dynamics Simulation of Peptide Adsorption on High-Density Polyethylene and Amorphous Silica

James Synder (Clemson University)

A nonbonded parameter set (i.e., partial charge and Lennard-Jones parameters) compatible with the CHARMM protein force field was recently derived by our group to accurately simulate peptide adsorption behavior on high density polyethylene (HDPE), amorphous silica (glass) and poly(methyl methacrylate) (PMMA) surfaces. This parameter set was tuned to bring the calculated adsorption free energies for a set of ten small host-guest peptides on the surface into agreement with experimental values within approximately 0.5 kcal/mol. This was accomplished using a modified version of CHARMM, entitled dual force-field CHARMM (Biswas et al., J. Comput. Chem. 2012), which permits an independent set of interfacial force field nonbonded parameters to be used to represent interphase (i.e., protein-surface, water-surface) interactions while using the standard CHARMM protein force field to separately represent intraphase interactions. The validity of this tuned parameter set is currently being tested by performing REMD and TIGER2 simulations for a solvated system composed of the proteins lysozyme and ribonuclease over silica glass surfaces. Characteristic conformational features of the proteins associated with adsorption (e.g., changes in secondary and tertiary structure and changes in residue solvent accessibility) on the surface are being determined from an analysis of the ensemble averages from the simulations for comparison with experimental results. Secondary structure information are being compared with experimental results obtained from circular dichroism (CD) spectropolarimetry studies, while changes in solvent accessibility are being compared with experimental results from amino acid side-chain modification and mass spectrometry.

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