Development of novel statistical potentials describing cation-π interactions in proteins and comparison with semiempirical and quantum chemistry approaches
Development of novel statistical potentials describing cation-π interactions in proteins and comparison with semiempirical and quantum chemistry approaches
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DOI：
10.1021/ci050395b
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发表时间：
2006-03-01
影响因子：
5.6
通讯作者：
Rooman, M
中科院分区：
文献类型：
--
作者：
Gilis, D;Biot, C;Rooman, M
提出了从已知蛋白质结构中获得的新的统计势。它们被设计用来描述带正电的氨基酸或带有部分带电的氨基的氨基酸与芳香族部分之间的阳离子-pi和氨基-pi相互作用。这些势能是基于残基类型被某一空间距离隔开或具有给定的相对取向的倾向。几个这样的势，描述了残基类型、距离和取向之间的不同类型的相关性，被导出并以一种最大化它们的信息量和最小化它们的冗余的方式组合。为了测试这些势描述阳离子-pi和氨基-pi体系的能力，我们将它们的能量与CHARMM分子力学力场计算的能量、Hartree-Fock水平(HF)和Moller-Plesset微扰理论(MP2)的二阶量子化学计算的能量进行了比较。后一种计算是在气相和丙酮中进行的，以模拟蛋白质环境的平均介电常数。用我们最好的统计势和气相HF或MP2计算的能量，当在统计势中考虑一个侧链自由度时，相关系数高达0.96，当使用完全简化的模型，不考虑所有侧链自由度时，相关系数高达0.94。这些势的表现与CHARMM分子力学力场一样好，甚至更好，后者使用了更详细的蛋白质表示。我们的阳离子-pi统计势的良好性能表明它们在蛋白质结构和稳定性预测以及蛋白质设计中的应用。
Novel statistical potentials derived from known protein structures are presented. They are designed to describe cation-pi and amino-pi interactions between a positively charged amino acid or an amino acid carrying a partially charged amino group and an aromatic moiety. These potentials are based on the propensity of residue types to be separated by a certain spatial distance or to have a given relative orientation. Several such potentials, describing different kinds of correlations between residue types, distances, and orientations, are derived and combined in a way that maximizes their information content and minimizes their redundancy. To test the ability of these potentials to describe cation-pi and amino-pi systems, we compare their energies with those computed with the CHARMM molecular mechanics force field and with quantum chemistry calculations at the Hartree-Fock level (HF) and at the second order of the Moller-Plesset perturbation theory (MP2). The latter calculations are performed in the gas phase and in acetone, in order to mimic the average dielectric constant of protein environments. The energies computed with the best of our statistical potentials and with gas-phase HF or MP2 show correlation coefficients up to 0.96 when considering one side-chain degree of freedom in the statistical potentials and up to 0.94 when using a totally simplified model excluding all side-chain degrees of freedom. These potentials perform as well as, or better than, the CHARMM molecular mechanics force field that uses a much more detailed protein representation. The good performance of our cation-pi statistical potentials suggests their utility in protein structure and stability prediction and in protein design.