title: Constant pH molecular dynamics (CpHMD) and molecular docking studies of CquiOBP1 pH-induced ligand releasing mechanism.
abstract: The odorant binding protein of Culex quinquefasciatus (CquiOBP1), expressed on the insect antenna, is crucial for the investigation of trapping baited with oviposition semi-chemicals and controlling mosquito populations. The acidic titratable residues pKa prediction and the ligand binding poses investigation in two systems (pH 7 and pH 5) are studied by constant pH molecular dynamics (CpHMD) and molecular docking methods. Research results reveal that the change of the protonation states would disrupt some important H-bonds, such as Asp 66-Asp 70, Glu 105-Asn 102, etc. The cleavage of these H-bonds leads to the movement of the relative position of hydrophobic tunnel, N- and C- termini loops and pH-sensing triad (His23-Tyr54-Val125) in acid solution. Ligand MOP has lower affinity and shows different binding poses to protein CquiOBP1 at pH 5. This ligand may be released from another tunnel between helices α3 and α4 in acidic environment. However, it would bind to the protein with high affinity in neutral environment. This work could provide more penetrating understanding of the pH-induced ligand-releasing mechanism.
authors.affiliation: State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, People's Republic of China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Chu
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Zhang
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Zheng
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Yun-Jian
authors.initials: YJ
authors.lastname: Wu
authors.forename: Qiao
authors.initials: Q
authors.lastname: Xue
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D057506:Arthropod Antennae / Q000378:metabolism; D003465:Culex / Q000378:metabolism; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D019476:Insect Proteins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D018035:Receptors, Odorant / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D019476:Insect Proteins; D008024:Ligands; D018035:Receptors, Odorant; C045648:odorant-binding protein