Conformational Changes of Protein Analyzed Based on Structural Perturbation Method
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ORIGINAL RESEARCH
Conformational Changes of Protein Analyzed Based on Structural Perturbation Method Kilho Eom1 Received: 3 November 2020 / Revised: 3 November 2020 / Accepted: 9 November 2020 © Korean Multi-Scale Mechanics (KMSM) 2020
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. Keywords Elastic network model · Conformational transition · Structural perturbation · Low-frequency normal modes
Introduction Proteins perform their biological functions through their conformational changes (i.e. structural changes) due to ligand-binding [1]. This indicates the necessity of characterizing the conformational changes of proteins. Though atomistic simulations have played a crucial role in studying the conformational dynamics of proteins [2–4], they are computationally restrictive in analyzing the dynamics of large protein complexes and their conformational changes. Specifically, spatial and temporal scales for the conformational changes of large protein complexes are usually inaccessible with atomistic molecular dynamics simulations. For last decades, efforts have been made to develop a coarse-grained model for computationally efficient analysis of the conformational dynamics of large protein complexes [5–8]. One of widely used coarse-grained models is an elastic network model (ENM) [9–14], which regards a protein structure as a network of elastic springs. The robustness of ENM is * Kilho Eom [email protected] 1
Biomechanics Laboratory, College of Sport Science, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
attributed to its ability to depict the protein’s structural feature (i.e. native topology) governing the protein dynamics. Specifically, a previous study Lu et al. [15] reports that the low-frequency normal modes of a protein are well conserved as long as the native topology of a protein is preserved, which indicates the robustness of ENM in capturing the dynamic characteristics of proteins. More interestingly, the low-frequency normal modes of proteins, obtained from ENM, have been shown to highly correlate with their conformational changes [12
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