Insights into Allostery from the Local Elastic Constants of a Protein

Abstract

Allostery connects subtle changes in a protein's potential energy surface (induced by perturbations such as ligand-binding) to significant changes in its function. Understanding this phenomenon and predicting its occurrence are major goals of current research on biophysics and molecular biology. Here we introduce a novel approach for studying complex structural transformations such as those typical for allostery. We show that the calculation and analysis of atomic elastic constants of a known allosterically regulated protein, lac repressor, highlights regions that are particularly prone to suffer structural deformation and are experimentally linked to allosteric function. The calculations are based on a high resolution, all-atom description of the protein, but are computationally inexpensive when compared to currently used methods that employ the same resolution. We also show that, for the present system, lower resolution models yield qualitatively different results, indicating the importance of adequately describing the local environment surrounding the different parts of the protein.