title: Functional loop dynamics of the streptavidin-biotin complex.
abstract: Accelerated molecular dynamics (aMD) simulation is employed to study the functional dynamics of the flexible loop(3-4) in the strong-binding streptavidin-biotin complex system. Conventional molecular (cMD) simulation is also performed for comparison. The present study reveals the following important properties of the loop dynamics: (1) The transition of loop(3-4) from open to closed state is observed in 200 ns aMD simulation. (2) In the absence of biotin binding, the open-state streptavidin is more stable, which is consistent with experimental evidences. The free energy (ΔG) difference is about 5 kcal/mol between two states. But with biotin binding, the closed state is more stable due to electrostatic and hydrophobic interactions between the loop(3-4) and biotin. (3) The closure of loop(3-4) is concerted to the stable binding of biotin to streptavidin. When the loop(3-4) is in its open-state, biotin moves out of the binding pocket, indicating that the interactions between the loop(3-4) and biotin are essential in trapping biotin in the binding pocket. (4) In the tetrameric streptavidin system, the conformational change of the loop(3-4) in each monomer is independent of each other. That is, there is no cooperative binding for biotin bound to the four subunits of the tetramer.
authors.affiliation: State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Chemistry, New York University.
authors.forename: Yongle
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China [2] Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, China [3] NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, China 200062.
authors.forename: Changge
authors.initials: C
authors.lastname: Ji
authors.affiliation: 1] State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China [2] NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, China 200062.
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D001710:Biotin / Q000031:analogs & derivatives* / Q000737:chemistry; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; C066114:biotin-streptavidin complex; D001710:Biotin