title: Function changing mutations in glucocorticoid receptor evolution correlate with their relevance to mode coupling.
abstract: Nonlinear effects in protein dynamics are expected to play role in function, particularly of allosteric nature, by facilitating energy transfer between vibrational modes. A recently proposed method focusing on the non-Gaussian shape of the configurational population near equilibrium projects this information onto real space in order to identify the aminoacids relevant to function. We here apply this method to three ancestral proteins in glucocorticoid receptor (GR) family and show that the mutations that restrict functional activity during GR evolution correlate significantly with locations that are highlighted by the nonlinear contribution to the near-native configurational distribution. Our findings demonstrate that the analysis of nonlinear effects in protein dynamics can be harnessed into a predictive tool for functional site determination.
authors.affiliation: Department of Theory & Biosystems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, Potsdam, 14476, Germany.|Colleges of Sciences, Koç University, Sar Iyer, İstanbul, 34450, Turkey.
authors.forename: Batuhan
authors.initials: B
authors.lastname: Kav
authors.affiliation: Colleges of Sciences, Koç University, Sar Iyer, İstanbul, 34450, Turkey.|School of Informatics and Computing, Bioinformatics Track, Indiana University, Bloomington, Indiana, 47405, USA.
authors.forename: Murat
authors.initials: M
authors.lastname: Öztürk
authors.affiliation: Colleges of Sciences, Koç University, Sar Iyer, İstanbul, 34450, Turkey.
authors.forename: Alkan
authors.initials: A
authors.lastname: Kabakçιoğlu
mesh_terms: D000494:Allosteric Regulation; D019143:Evolution, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation / Q000235:genetics*; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D011965:Receptors, Glucocorticoid
keywords: : mode coupling; allostery; anharmonicity; glucocorticoid receptors; molecular dynamics; protein evolution