title: Identification of thermostabilizing mutations for a membrane protein whose three-dimensional structure is unknown.
abstract: We recently developed a physics-based method for identifying thermostabilizing mutations of a membrane protein. The method uses a free-energy function F where the importance of translational entropy of hydrocarbon groups within the lipid bilayer is emphasized. All of the possible mutations can rapidly be examined. The method was illustrated for the adenosine A2areceptor (A2aR) whose three-dimensional (3D) structure experimentally determined was utilized as the wild-type structure. Nine single mutations and a double mutation predicted to be stabilizing or destabilizing were checked by referring to the experimental results: The success rate was remarkably high. In this work, we postulate that the 3D structure of A2aR is unknown. We construct candidate models for the 3D structure using the homology modeling and select the model giving the lowest value to the change in F on protein folding. The performance achieved is only slightly lower than that in the recent work. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Fundamental Energy Science, Graduate School of Energy Science, Kyoto University, Uji, Kyoto, 611-0011, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kajiwara
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage, Chiba, 263-8522, Japan.|Molecular Chirality Research Center, Chiba University, 1-33 Yayoi-cho, Inage, Chiba, 263-8522, Japan.|Laboratory for Complex Energy Processes Section, Institute of Advanced Energy, Kyoto University, Uji, Kyoto, 611-0011, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage, Chiba, 263-8522, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Takamuku
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage, Chiba, 263-8522, Japan.|Molecular Chirality Research Center, Chiba University, 1-33 Yayoi-cho, Inage, Chiba, 263-8522, Japan.|JST, PRESTO, 1-33 Yayoi-cho, Inage, Chiba, 263-8522, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murata
authors.affiliation: Laboratory for Complex Energy Processes Section, Institute of Advanced Energy, Kyoto University, Uji, Kyoto, 611-0011, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kinoshita
mesh_terms: D019295:Computational Biology; D003198:Computer Simulation; D019277:Entropy; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D008958:Models, Molecular; D008962:Models, Theoretical; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D021281:Quantitative Structure-Activity Relationship; D043705:Receptor, Adenosine A2A / Q000737:chemistry* / Q000235:genetics*; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D043705:Receptor, Adenosine A2A
keywords: free energy function; hydrogen bonding; lipid bilayer; protein; solvation entropy