【摘要】 通过分析蛋白质-蛋白质间的静电、疏水作用和熵效应与相对于晶体结构的蛋白质主链原子的均方根偏差(RMSD)的相关性,定量地考查了它们在蛋白质-蛋白质对接中作为打分函数评价近天然构象的能力。对7个蛋白质复合物体系的分析表明,就水化能而言,原子接触势模型(ACE)优于原子水化参数模型(ASP),且修正的ACE模型具有更好的评价近天然构象的能力;水化能与静电能结合对评价能力有进一步的提高。最后,我们将静电和修正的ACE水化能结合作为打分函数用于36个蛋白质复合物体系的对接研究,进一步证实了这两种能量项的组合能有效地将近天然结构从分子对接模式中区分出来。更多还原

【Abstract】 Binding free energy potentials, combining molecular mechanics with empirical solvation and entropic terms, are used to discriminate near-native conformations from slightly misdocked protein-protein decoys. It is of interest to determine the contributions of individual binding free energy terms and their combinations to the discriminative power of the potential. This is achieved in terms of quantitative measure of the correlation coefficient between binding free energy and the root mean square deviation (RMSD) of backbone atoms from the native complex structure. From the results, the discrimination improves if the binding free energy expression includes the electrostatic energy and an empirical solvation term, with the structure-based atomic contact potential (ACE) providing much better discrimination than the atomic solvation parameter model (ASP). Moreover, obvious improvement is obtained when using the modified atomic contact potential is used. By scoring test for 36 protein-protein docking cases, the results further indicate that the combination of the electrostatic energy and the modified atomic contact potential (ACE) is of much better discriminative power and can be used to score the putative binding modes in protein-protein docking.更多还原