CALCULATIONS OF ENZYMATIC-REACTIONS - CALCULATIONS OF PKA, PROTON-TRANSFER REACTIONS, AND GENERAL ACID CATALYSIS REACTIONS IN ENZYMES
CALCULATIONS OF ENZYMATIC-REACTIONS - CALCULATIONS OF PKA, PROTON-TRANSFER REACTIONS, AND GENERAL ACID CATALYSIS REACTIONS IN ENZYMES
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DOI：
10.1021/bi00514a028
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发表时间：
1981-01-01
期刊：
影响因子：
2.9
通讯作者：
WARSHEL, A
中科院分区：
文献类型：
--
作者：
WARSHEL, A
一种方法，允许相关的可用的X射线数据与酶反应的活化自由能。该方法是基于经验价键的方法，使用实验信息来评估参与反应的价键共振形式的能量，然后计算酶和溶液中离子共振形式的环境依赖性稳定化，并将它们与酶的速率加速相关联。该方法是可靠的，因为它是基于校准的潜在表面的溶液实验和转移的校准表面的酶活性位点，仅使用简单的计算静电相互作用。该方法和直观的价键描述键断裂，键的反应之间的密切关系提供了一个新的洞察酶促反应，描述它们之间的交叉共价和离子价键共振形式。这种描述将酶活性位点对离子共振形式的稳定与酶催化活性相关联。本文考虑了几种酶过程的能量学，包括酶活性位点中酸性基团的电离，酶和溶液中离子对的稳定性，质子转移反应和一般的酸催化反应。计算支持的想法，酶可以被视为超溶剂，稳定（溶剂化）离子过渡态更有效地比水溶液。
A method that allows the correlation of available X-ray data with activation-free energies of enzymatic reactions is presented. This method is based on the empirical valence bond approach which uses experimental information to evaluate the energies of the valence bond resonance forms involved in a reaction and then calculates the environment-dependent stabilizations of the ionic resonance forms in the enzyme and in solution, and correlates them with the rate acceleration by the enzyme. The method is reliable since it is based on calibration of potential surfaces by solution experiments and transfer of the calibrated surfaces to the enzyme active site, using only simple calculations of electrostatic interactions. The close relation between the method and the intuitive valence bond description of bond-breaking, bond-making reactions provides a new insight into enzymatic reactions, describing them as crossings between covalent and ionic valence bond resonance forms. Such a description correlates the stabilization of the ionic resonance forms by the enzyme active site with the enzyme catalytic activity. The paper considers the energetics of several enzymatic processes, including ionization of acidic groups in enzyme active sites, stability of ion pairs in enzymes and in solutions, proton transfer reactions, and general acid catalysis reactions. The calculations support the idea that enzymes can be viewed as supersolvents that stabilize (solvate) ionic transition states more effectively than do aqueous solutions.