丝氨酸蛋白酶的从头算分子动力学研究
Serine Proteases: an Ab Initio Molecular Dynamics Study
摘要：
在丝氨酸蛋白酶（SP）中，His-57和Asp-102之间的氢键以及Gly-193和过渡态中间体之间的氢键对酶的功能起着至关重要的作用。为了阐明这些相互作用的性质，我们进行了从头算分子动力学模拟的反应中间体和弹性蛋白酶（一种蛋白质属于SP家族）之间的加合物的复合物。我们的计算表明，存在一个低-势垒之间的H-键的His-57和Asp-102，在完全符合与NMR实验酶-过渡态类似物复合物。与从头算分子动力学模拟的底物-酶加合物的模型上的比较表明，甘氨酸-193-诱导的强稳定的中间体是通过电荷/偶极相互作用，而不是通过H-键如前所述。在计算中包含蛋白质电场不会显著影响电荷分布。
英文摘要：
In serine proteases (SP's), the H-bond between His-57 and Asp-102, and that between Gly-193 and the transition state intermediate play a crucial role for enzymatic function. To shed light on the nature of these interactions, we have carried out ab initio molecular dynamics simulations on complexes representing adducts between the reaction intermediate and elastase (one protein belonging to the SP family). Our calculations indicate the presence of a low--barrier H-bond between His-57 and Asp-102, in complete agreement with NMR experiments on enzyme--transition state analog complexes. Comparison with an ab initio molecular dynamics simulation on a model of the substrate--enzyme adduct indicates that the Gly-193--induced strong stabilization of the intermediate is accomplished by charge/dipole interactions and not by H-bonding as previously suggested. Inclusion of the protein electric field in the calculations does not affect significantly the charge distribution.
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