Development and validation of an empirical free energy function for calculating protein-protein binding free energy surfaces
Development and validation of an empirical free energy function for calculating protein-protein binding free energy surfaces
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DOI：
10.1016/j.bpc.2008.10.007
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发表时间：
2009-02-01
影响因子：
3.8
通讯作者：
Audie, Joseph
中科院分区：
文献类型：
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作者：
Audie, Joseph
在之前的一篇论文中，我们描述了一个新的经验自由能函数，该函数用于准确预测31个蛋白质-蛋白质复合体的实验结合自由能，其范围约为1.0kcal。在这里，我们扩展了工作，并表明该函数更新版本可用于(1)准确地预测自然结合自由能和(2)以物理现实的方式对结晶学、自然类和非自然结合模式进行排序。修改后的函数包括一些术语，旨在捕获非本机接口的一些不利交互特征。用该函数计算了21个蛋白质络合物的一维结合自由能表面。在大约90%的测试案例中，该函数用于将类自然和晶体结合模式放置在全球自由能最小值中。我们的分析进一步表明，埋藏的氢键可能是区分自然和非自然相互作用的关键。就我们所知，我们的函数是同类中唯一的一个，一个单一的表达式，可以用来准确计算大量蛋白质的天然和非天然结合自由能。鉴于本文提出的令人鼓舞的结果，未来的工作将集中在改进功能并将其应用于蛋白质-蛋白质对接问题。(C)2008爱思唯尔B.V.保留所有权利。
In a previous paper, we described a novel empirical free energy function that was used to accurately predict experimental binding free energies for a diverse test set of 31 protein-protein complexes to within approximate to 1.0 kcal. Here, we extend that work and show that an updated version of the function can be used to (1) accurately predict native binding free energies and (2) rank crystallographic, native-like and non-native binding modes in a physically realistic manner. The modified function includes terms designed to capture some of the unfavorable interactions that characterize non-native interfaces. The function was used to calculate one-dimensional binding free energy surfaces for 21 protein complexes. In roughly 90% of the cases tested, the function was used to place native-like and crystallographic binding modes in global free energy minima. Our analysis further suggests that buried hydrogen bonds might provide the key to distinguishing native from non-native interactions. To the best of our knowledge our function is the only one of its kind, a single expression that can be used to accurately calculate native and non-native binding free energies for a large number of proteins. Given the encouraging results presented in this paper, future work will focus on improving the function and applying it to the protein-protein docking problem. (C) 2008 Elsevier B.V. All rights reserved.