(151c) A Novel, Coarse-Grain Model for Chemically-Specific, Protein-Surface Interactions: Validation and Application

Protein-surface interactions are key phenomena in a variety of technologies, but a complete, fundamental understanding of the underlying biophysics involved remains elusive.  In recent years, coarse-grain 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. While many insights into the topic have been gained with this approach, studies to date have suffered from a major limitation: the surface has been modeling in only a rudimentary way even by coarse-graining standards. Specifically, the vast majority of all coarse-grain simulations have used either a hard surface or a short-range, repulsive surface which has interacted with all sites in the protein the same way regardless of the chemistry of the surface or the identity of the residues in the protein.

Moving the research to the next level requires a better model for the system that takes into account sequence-specific, residue-level interactions between the protein and the surface.  We have spent the last several years developing such a model.  The first version of the model showed promise, but we encountered several challenges that required taking a slightly different approach. This new formalism maintains the computational efficiency characteristic of all coarse-grain representations, but takes into account the hydrophobic nature of both the surface and the individual residues comprising the protein.

This presentation will outline the latest version of the model.  The limitations of previous approaches will be explained first followed by a description of the current functional form of the model.  The details of the parameterization against experimental adsorption data for small peptides will then be explained.  This will be followed by results from simulations used to validate the transferability of the model to larger, more-relevant proteins such as lysozyme and alpha-amylase.  The agreement between the simulation and experimental data for these cases is remarkable and is obtained without reparameterization. The presentation will end with a side-by-side comparison of folding mechanisms for various proteins produced using the old and the new models. Taken as a whole, the results offer significant hope that the rational design of protein-surface technologies is possible.