Solvent Binding Analysis and Computational Alanine Scanning of the Bovine Chymosin-Bovine κ-Casein Complex Using Molecular Integral Equation Theory.
Solvent Binding Analysis and Computational Alanine Scanning of the Bovine Chymosin-Bovine κ-Casein Complex Using Molecular Integral Equation Theory.
复制标题
使用分子积分方程理论对牛凝乳酶-牛 γ-酪蛋白复合物进行溶剂结合分析和计算丙氨酸扫描
DOI：
10.1021/ct400605x
复制
发表时间：
2013
影响因子：
5.5
通讯作者：
Fedorov
中科院分区：
文献类型：
--
作者：
Palmer;Sørensen;Schiøtt;Fedorov
我们证明了用分子积分方程式理论可以准确有效地计算模型蛋白质-多肽复合体(牛凝乳蛋白-牛κ-酪蛋白复合体)的单点突变的相对结合热力学。计算结果与隐式连续介质溶剂化模型的计算结果基本一致。然而，与隐式连续介质模型不同，分子积分方程式理论提供了有关溶剂密度分布的有用信息。我们发现，根据分子积分方程论计算的密度分布函数，可以快速、准确地识别实验观察到的牛凝乳酶表面的水结合部位。牛凝乳酶-牛κ-酪蛋白复合体具有工业应用价值，因为牛凝乳酶被广泛用于裂解牛κ-酪蛋白，并在加工乳制品生产中引发乳凝。根据最近的一项发现，骆驼凝乳酶是一种比牛凝乳酶更有效的凝血剂来解释这一结果。
We demonstrate that the relative binding thermodynamics of single-point mutants of a model protein–peptide complex (the bovine chymosin–bovine κ-casein complex) can be calculated accurately and efficiently using molecular integral equation theory. The results are shown to be in good overall agreement with those obtained using implicit continuum solvation models. Unlike the implicit continuum models, however, molecular integral equation theory provides useful information about the distribution of solvent density. We find that experimentally observed water-binding sites on the surface of bovine chymosin can be identified quickly and accurately from the density distribution functions computed by molecular integral equation theory. The bovine chymosin–bovine κ-casein complex is of industrial interest because bovine chymosin is widely used to cleave bovine κ-casein and to initiate milk clotting in the manufacturing of processed dairy products. The results are interpreted in light of the recent discovery that camel chymosin is a more efficient clotting agent than bovine chymosin for bovine milk.