title: Prediction of allosteric sites on protein surfaces with an elastic-network-model-based thermodynamic method.
abstract: Allostery is a rapid and efficient way in many biological processes to regulate protein functions, where binding of an effector at the allosteric site alters the activity and function at a distant active site. Allosteric regulation of protein biological functions provides a promising strategy for novel drug design. However, how to effectively identify the allosteric sites remains one of the major challenges for allosteric drug design. In the present work, a thermodynamic method based on the elastic network model was proposed to predict the allosteric sites on the protein surface. In our method, the thermodynamic coupling between the allosteric and active sites was considered, and then the allosteric sites were identified as those where the binding of an effector molecule induces a large change in the binding free energy of the protein with its ligand. Using the proposed method, two proteins, i.e., the 70 kD heat shock protein (Hsp70) and GluA2 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, were studied and the allosteric sites on the protein surface were successfully identified. The predicted results are consistent with the available experimental data, which indicates that our method is a simple yet effective approach for the identification of allosteric sites on proteins.
authors.affiliation: College of Science, Yanshan University, Qinhuangdao 066004, China.
authors.forename: Ji Guo
authors.initials: JG
authors.lastname: Su
authors.affiliation: Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Institute of Biophysics, Dezhou University, Dezhou 253023, China.
authors.forename: Li Sheng
authors.initials: LS
authors.lastname: Qi
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100022, China.
authors.forename: Chun Hua
authors.initials: CH
authors.lastname: Li
authors.affiliation: College of Science, Yanshan University, Qinhuangdao 066004, China.
authors.forename: Yan Ying
authors.initials: YY
authors.lastname: Zhu
authors.affiliation: College of Science, Yanshan University, Qinhuangdao 066004, China.
authors.forename: Hui Jing
authors.initials: HJ
authors.lastname: Du
authors.affiliation: College of Science, Yanshan University, Qinhuangdao 066004, China.
authors.forename: Yan Xue
authors.initials: YX
authors.lastname: Hou
authors.affiliation: College of Science, Yanshan University, Qinhuangdao 066004, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Hao
authors.affiliation: Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Institute of Biophysics, Dezhou University, Dezhou 253023, China.
authors.forename: Ji Hua
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000495:Allosteric Site; D000818:Animals; D020134:Catalytic Domain; D004548:Elasticity; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2