Computational methods for the incorporation of protein unfolding pathways and kinetics in protein design

Abstract

Hydrophobic collapse is one of the main driving forces of protein folding. As such, accurately modeling solvation effects and electrostatics is a key component of any energy function. This can be achieved through explicitly modeling each solvent water molecule or by implicitly modeling the bulk solvent as a continuum. GeoFold utilizes a solvent accessible surface area (SAS) based implicit solvation model; however, it does not adequately capture the impact of exposure to solvent of hydrophobic vs hydrophilic residues. In this work, the WZS model is implemented, demonstrating improved accuracy in the prediction of unfolding rates in an 86-protein case study.