从对接结构中挑选近天然构象的新方法

分析了包含静电能(ΔEele)、去水化自由能(ΔGACE)以及范德华能(ΔEvdw)的打分函数在蛋白质－蛋白质对接中评价近天然构象的能力.对17种蛋白质复合物对接体系进行打分的结果表明，包含范德华能的打分函数（ΔEele＋ΔGACE＋ΔEvdw）比通常的打分函数（ΔEele、ΔGACE、ΔEele＋ΔGACE、ΔEele＋ΔEvdw、ΔGACE＋ΔEvdw）具有更好的区分近天然构象的能力.进一步的研究表明，优化（EM）对接体系后再进行打分，上面几种打分函数对对接结构的评价效果都有不同程度的改善，其中打分函数（ΔEele＋ΔGACE＋ΔEvdw）有更明显的改善.为了进一步确定候选结构中的近天然构象，以一种蛋白质复合物为例，对候选结构进行分子动力学（MD）模拟，根据MD轨迹中构象相对于初始构象的平方平均偏差（MSD）随时间的变化来辅助打分函数排除错误构象，得到了较好的结果.

A New Method to Select the Near-native Conformations from the Docked Structures

A scoring function that contains the electrostatic, desolvation and van der Waals energy was used to discriminate the near-native conformations in protein-protein docking. The analysis results of the docked structures for seventeen protein complexes showed that the scoring function including van der Waals energy（ΔEele＋ΔGACE＋ΔEvdw） had much more potentiality in distinguishing the near-native conformations from the incorrect ones compared with other scoring functions, such as ΔEele, ΔGACE, ΔEele＋ΔGACE, ΔEele＋ΔEvdw andΔGACE＋ΔEvdw. It was found that energy minimization could improve the discrimination results for all the scoring functions mentioned above to some extent, especially forΔEele＋ΔGACE＋ΔEvdw. Finally, to further determinate the near-native structure, we performed the molecular dynamics (MD) simulations for the candidate structures of 4INSXX. According to the variations of the mean square deviation (MSD) of the structures in MD trajectories relative to the initial structures, the false structures could be excluded.