title: The origin of the cooperativity in the streptavidin-biotin system: A computational investigation through molecular dynamics simulations.
abstract: Previous experimental study measuring the binding affinities of biotin to the wild type streptavidin (WT) and three mutants (S45A, D128A and S45A/D128A double mutant) has shown that the loss of binding affinity from the double mutation is larger than the direct sum of those from two single mutations. The origin of this cooperativity has been investigated in this work through molecular dynamics simulations and the end-state free energy method using the polarized protein-specific charge. The results show that this cooperativity comes from both the enthalpy and entropy contributions. The former contribution mainly comes from the alternations of solvation free energy. Decomposition analysis shows that the mutated residues nearly have no contributions to the cooperativity. Instead, N49 and S88, which are located at the entry of the binding pocket and interact with the carboxyl group of biotin, make the dominant contribution among all the residues in the first binding shell around biotin.
authors.affiliation: State Key Laboratory of Precision Spectroscopy, School of Physics and Materials Science, East China Normal University, Shanghai 200062, China.
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Physics, School of Physics and Materials Science, East China Normal University, Shanghai 200062, China.|NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China.
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Precision Spectroscopy, School of Physics and Materials Science, East China Normal University, Shanghai 200062, China.|NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Mei
mesh_terms: D001665:Binding Sites; D001710:Biotin / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D019809:Streptavidin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001710:Biotin; D019809:Streptavidin