Roy Arijit, Taraphder Srabani
Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
J Phys Chem B. 2009 Sep 17;113(37):12555-64. doi: 10.1021/jp9010982.
We report here a transition path sampling study of the conformational fluctuation of His-64 that is known to be important in the enzymatic catalysis of human carbonic anhydrase II. The dynamical transition between experimentally detected conformations of His-64 could not be observed using classical molecular dynamics trajectories extended to 3.5 ns, indicating the transition to be rare on the time scale of molecular dynamics. Using the transition path sampling method, an ensemble of transition paths between these two conformers has been generated and analyzed in detail to identify the mechanism of coupling of His-64 to its neighboring residues during the conformational transition. It is found that both Asn-62 and Tyr-7 may contribute toward retaining the His-64 residue in its outward conformation. Trp-5, on the other hand, shows marked motions at the transition state. The number of water molecules inside a part of the active site cavity and the corresponding cavity volume are also found to vary coupled to the His-64 conformational dynamics.
我们在此报告一项关于His-64构象波动的过渡路径抽样研究，已知His-64在人碳酸酐酶II的酶催化中很重要。使用扩展至3.5 ns的经典分子动力学轨迹无法观察到实验检测到的His-64构象之间的动态转变，这表明该转变在分子动力学时间尺度上很少见。使用过渡路径抽样方法，已生成并详细分析了这两种构象异构体之间的一组过渡路径，以确定His-64在构象转变过程中与其相邻残基耦合的机制。发现Asn-62和Tyr-7都可能有助于将His-64残基保持在其向外的构象中。另一方面，Trp-5在过渡态表现出明显的运动。还发现活性位点腔一部分内的水分子数量和相应的腔体积会随着His-64构象动力学而变化。
