摘要
Takeout(To)蛋白广泛存在于各类昆虫体内,与昆虫体内很多生理过程和行为有关。To蛋白能够将运送小分子到特定的组织中,完成相应信号传导过程。然而,其配体分子的释放和结合机制至今不明。文章中,我们通过分子动力学模拟、拉伸动力学、伞形抽样的方法揭示了这个过程和释放途径。结果显示,蛋白的α4-side片段是唯一的的开关,用来调节小分子的结合与释放。通过结合平均势计算和残基交叉相关性计算,得出小分子与To蛋白的结合是一个构象选择的过程。并且To蛋白的构象变化和疏水相互作用都是小分子结合与释放的重要因素。
Takeout(To) proteins exist in a diverse range of insect species.They are involved in many important processes of insect physiology and behaviours.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 α 4-side of the protein is the unique gate for the ligand binding and release.By using the potential of mean force(PMF) 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.
引文
[1]Hamiaux,C,Basten,L.,Greenwood,D.R.,Baker,E.N.,&Newcomb,R.D.2013,J Struct Biol,182(3),259-263.
[2]Hamiaux,C,Stanley,D.,Greenwood,D.R.,Baker,E.N.,&Newcomb,R.D.2009,J Biol Chem,284(6),3496-3503.