MacKerell A D, Rigler R, Nilsson L, Heinemann U, Saenger W
Department of Medical Biophysics, Karolinska Institutet, Stockholm, Sweden.
Eur Biophys J. 1988;16(5):287-97. doi: 10.1007/BF00254065.
Molecular dynamics simulations in vacuum and with a water sphere around the active site were performed on the 2'GMP-RNase T1 complex. The presence of water led to the maintenance of the 2'-GMP-RNase T1 interactions as compared to the X-ray structure, including the hydrogen bonds implicated in the enzyme-inhibitor recognition process. The sidechain of His92 in the molecular dynamics water simulation, however, hydrogen bonds directly to the phosphate of 2'GMP in contrast to the X-ray structure but in support of the role of that residue in the enzyme's catalytic mechanism. Fluctuations of active-site residues are not strongly influenced by water, possibly owing to the exclusion of water by the bound 2'GMP, which did show an increase in mobility. Analysis of the 2'GMP-RNase T1 interactions versus time reveal an equilibrium fluctuation in the presence of water, leading to a less favorable 2'GMP-RNase T1 interaction energy, suggesting a possible relationship between picosecond fluctuations and inhibitor dissociation occurring in the millisecond time domain.
对2'-GMP-RNase T1复合物进行了真空以及活性位点周围有一个水球环境下的分子动力学模拟。与X射线结构相比，水的存在导致2'-GMP与RNase T1之间的相互作用得以维持，包括参与酶-抑制剂识别过程的氢键。然而，在分子动力学水模拟中，His92的侧链与2'-GMP的磷酸基团直接形成氢键，这与X射线结构不同，但支持了该残基在酶催化机制中的作用。活性位点残基的波动受水的影响不大，这可能是由于结合的2'-GMP对水的排斥作用，不过2'-GMP的流动性确实有所增加。对2'-GMP与RNase T1相互作用随时间的分析表明，在有水存在的情况下存在平衡波动，导致2'-GMP与RNase T1的相互作用能更不利，这表明皮秒级波动与毫秒时域内发生的抑制剂解离之间可能存在关联。
