Toward computer-aided site-directed mutagenesis of enzymes.
Toward computer-aided site-directed mutagenesis of enzymes.
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走向计算机辅助的酶定点诱变。
DOI：
10.1073/pnas.83.11.3806
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发表时间：
1986
影响因子：
11.1
通讯作者：
Sussman,F
中科院分区：
文献类型：
--
作者：
Warshel,A;Sussman,F
初步尝试模拟大鼠胰蛋白酶定点诱变观察到的效果，给人以鼓舞人心的结果。的计算重现在半定量的方式观察到的变化，在活化势垒的限速步骤酰胺水解。这一结果，这不需要任何可调的参数，表明我们的方法可以提供一个可靠的基础，计算机辅助酶的设计。除了潜在的实用价值的计算，他们提供了重要的机械信息-也就是说，在胰蛋白酶的催化效果的变化似乎几乎完全是由于在离子配置的静电稳定的变化。这支持了静电效应是酶催化中的主要因素的观点。
A preliminary attempt to simulate the observed effect of a site-directed mutagenesis of rat trypsin gives encouraging results. The calculations reproduce in a semiquantitative way the observed change in the activation barrier of the rate-limiting step of amide hydrolysis. This result, which did not require any adjustable parameters, indicates that our method may provide a reliable basis for computer-aided enzyme design. In addition to the potentially practical value of the calculations, they provide important mechanistic information--that is, the change in the catalytic effect in trypsin appears to be almost exclusively due to the change in the electrostatic stabilization of the ionic configurations. This supports the view that electrostatic effects are the major factor in enzyme catalysis.
通过蛋白质工程大幅增加酶与底物的亲和力
影响因子：
64.8
作者：
A. Wilkinson;A. Fersht;D. Blow;P. Carter;G. Winter
通讯作者：
G. Winter