Identification of key residues in protein functional movements by using molecular dynamics simulations combined with a perturbation-response scanning method

Abstract

The realization of protein functional movement is usually accompanied by specific conformational changes, and there exist some key residues that mediate and control the functional motions of proteins in the allosteric process. In the present work, the perturbation-response scanning method developed by our group was combined with the molecular dynamics (MD) simulation to identify the key residues controlling the functional movement of proteins. In our method, a physical quantity that is directly related to protein specific function was introduced, and then based on the MD simulation trajectories, the perturbation-response scanning method was used to identify the key residues for functional motions, in which the residues that highly correlated with the fluctuation of the function-related quantity were identified as the key residues controlling the specific functional motions of the protein. Two protein systems, i.e., the heat shock protein 70 and glutamine binding protein, were selected as case studies to validate the effectiveness of our method. Our calculated results are in good agreement with the experimental results. The location of the key residues in the two proteins are similar, indicating the similar mechanisms behind the performance of their biological functions.