title: Investigations of Takeout proteins' ligand binding and release mechanism using molecular dynamics simulation.
abstract: Takeout (To) proteins exist in a diverse range of insect species. They are involved in many important processes of insect physiology and behaviors. As the ligand carriers, To proteins can transport the small molecule to the target tissues. However, ligand release mechanism of To proteins is unclear so far. In this contribution, the process and pathway of the ligand binding and release are revealed by conventional molecular dynamics simulation, steered molecular dynamics simulation and umbrella sampling methods. Our results show that the α4-side of the protein is the unique gate for the ligand binding and release. The structural analysis confirms that the internal cavity of the protein has high rigidity, which is in accordance with the recent experimental results. By using the potential of mean force calculations in combination with residue cross correlation calculation, we concluded that the binding between the ligand and To proteins is a process of conformational selection. Furthermore, the conformational changes of To proteins and the hydrophobic interactions both are the key factors for ligand binding and release.
authors.affiliation: a State Key Laboratory of Theoretical and Computational Chemistry , Institute of Theoretical Chemistry, Jilin University , Changchun 130023 , People's Republic of China.
authors.forename: Huijing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: b College of Chemistry and Biology, Beihua University , Jilin 132013 , People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: a State Key Laboratory of Theoretical and Computational Chemistry , Institute of Theoretical Chemistry, Jilin University , Changchun 130023 , People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: a State Key Laboratory of Theoretical and Computational Chemistry , Institute of Theoretical Chemistry, Jilin University , Changchun 130023 , People's Republic of China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Liu
authors.affiliation: c Modern Experimental Technology Center (Management) , Henan Agricultural University , Zhengzhou , Henan 450002 , People's Republic of China.
authors.forename: Xianli
authors.initials: X
authors.lastname: Feng
authors.affiliation: a State Key Laboratory of Theoretical and Computational Chemistry , Institute of Theoretical Chemistry, Jilin University , Changchun 130023 , People's Republic of China.
authors.forename: Xuri
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008024:Ligands; D056004:Molecular Dynamics Simulation; D009036:Moths / Q000737:chemistry*; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms / Q000737:chemistry; D040681:Structural Homology, Protein; D013816:Thermodynamics
chemical_list: D029721:Drosophila Proteins; D008024:Ligands; D020033:Protein Isoforms; C411066:TO protein, Drosophila
keywords: conformational selection; molecular dynamics; steered molecular dynamics; takeout proteins; umbrella sampling