(721e) A Novel, Coarse-Grained Model for Capturing Residue-Level Hydrophobic Effects In Protein/Surface Interactions

Protein/surface interactions are important in a variety of fields and devices, but fundamental understanding of the relevant phenomena is still in its infancy. In recent years, coarse-grained protein and surface models have been the preferred tools to examine such systems due to resolution limitations of experimental techniques and computational demands of all-atom simulations.  This approach has provided many insights into the thermodynamic behavior of proteins on surfaces, but improvements in the description of the system are needed to advance the field to the next level.  Specifically, the current coarse-grained surface models are either purely repulsive or attractive to all of the sites in the protein regardless of the type of residue.  Neither the properties of the amino acids in the protein nor those of the chemical moieties on the surface are taken into account. This simplification, while a necessary first step, specifically neglects the hydrophobic effects which are key to the interaction of proteins with their surroundings. 

This presentation outlines the development of a new model which takes into account sequence-specific, residue-level interactions between the protein and the surface. Of particular importance is the fact that the new model allows the interaction to be tuned to reproduce any type of surface chemistry desired. Coarse-graining is maintained for computational efficiency as each residue of the protein remains a single interaction site, but hydrophobic effects and desolvation penalties between the residues of the protein and the surface are added.  The hydrophobic effects are included in a novel manner using the hydropathy index which is an experimentally-determined measure of the relative hydrophobicity of each amino acid.  The presentation will outline the functional form of the model, the parameterization of the model using experimental adsorption data, and the insights that are gained from using the new formalism compared to the previous approaches.