Conformational Changes of Protein Analyzed Based on Structural Perturbation Method

Abstract

Proteins perform their biological functions through their conformational changes due to ligand-binding. Though atomistic simulations have allowed for understanding the conformational dynamics of proteins, they are computationally restrictive in revealing the conformational transition pathway of proteins. In this work, we consider an elastic network model (ENM) with introducing the structural perturbation method, which mimics the breakage or formation of native contacts during the conformational changes, for gaining insight into the conformational transition pathway of proteins. It is shown that ENM with structural perturbation method enables the characterization of the conformational transition of adenylate kinase as a model protein. In addition, the low-frequency normal modes of adenylate kinase are found to play a role in its conformational transition. Our study sheds light on ENM with structural perturbation method for studying the conformational transitions of large protein complexes.