Northrup S H, Pear M R, Lee C Y, McCammon J A, Karplus M
Proc Natl Acad Sci U S A. 1982 Jul;79(13):4035-9. doi: 10.1073/pnas.79.13.4035.
A method is described for calculating the reaction rate in globular proteins of activated processes such as ligand binding or enzymatic catalysis. The method is based on the determination of the probability that the system is in the transition state and of the magnitude of the reactive flux for transition-state systems. An "umbrella sampling" simulation procedure is outlined for evaluating the transition-state probability. The reactive flux is obtained from an approach described previously for calculating the dynamics of transition-state trajectories. An application to the rotational isomerization of an aromatic ring in the bovine pancreatic trypsin inhibitor is presented. The results demonstrate the feasibility of calculating rate constants for reactions in proteins and point to the importance of solvent effects for reactions that occur near the protein surface.
本文描述了一种计算球状蛋白质中诸如配体结合或酶催化等活化过程反应速率的方法。该方法基于确定系统处于过渡态的概率以及过渡态系统反应通量的大小。概述了一种“伞形采样”模拟程序来评估过渡态概率。反应通量是通过先前描述的一种计算过渡态轨迹动力学的方法获得的。给出了该方法在牛胰蛋白酶抑制剂中芳环旋转异构化反应的应用。结果证明了计算蛋白质中反应速率常数的可行性，并指出了溶剂效应对于发生在蛋白质表面附近反应的重要性。
