Chuang Gwo-Yu, Kozakov Dima, Brenke Ryan, Comeau Stephen R, Vajda Sandor
Department of Biomedical Engineering, and Program in Bioinformatics, Boston University, Boston, Massachusetts, USA.
Biophys J. 2008 Nov 1;95(9):4217-27. doi: 10.1529/biophysj.108.135814. Epub 2008 Aug 1.
Decoys As the Reference State (DARS) is a simple and natural approach to the construction of structure-based intermolecular potentials. The idea is generating a large set of docked conformations with good shape complementarity but without accounting for atom types, and using the frequency of interactions extracted from these decoys as the reference state. In principle, the resulting potential is ideal for finding near-native conformations among structures obtained by docking, and can be combined with other energy terms to be used directly in docking calculations. We investigated the performance of various DARS versions for docking enzyme-inhibitor, antigen-antibody, and other type of complexes. For enzyme-inhibitor pairs, DARS provides both excellent discrimination and docking results, even with very small decoy sets. For antigen-antibody complexes, DARS is slightly better than a number of interaction potentials tested, but results are worse than for enzyme-inhibitor complexes. With a few exceptions, the DARS docking results are also good for the other complexes, despite poor discrimination, and we show that the latter is not a correct test for docking accuracy. The analysis of interactions in antigen-antibody pairs reveals that, in constructing pairwise potentials for such complexes, one should account for the asymmetry of hydrophobic patches on the two sides of the interface. Similar asymmetry does occur in the few other complexes with poor DARS docking results.
以诱饵作为参考态（DARS）是一种构建基于结构的分子间势的简单而自然的方法。其思路是生成大量具有良好形状互补性但不考虑原子类型的对接构象，并将从这些诱饵中提取的相互作用频率用作参考态。原则上，由此产生的势对于在对接获得的结构中找到近天然构象非常理想，并且可以与其他能量项结合，直接用于对接计算。我们研究了各种DARS版本在对接酶-抑制剂、抗原-抗体及其他类型复合物方面的性能。对于酶-抑制剂对，即使使用非常小的诱饵集，DARS也能提供出色的区分能力和对接结果。对于抗原-抗体复合物，DARS略优于一些测试的相互作用势，但结果比酶-抑制剂复合物的更差。除了少数例外情况，尽管区分能力较差，DARS对接结果对于其他复合物也很好，并且我们表明后者不是对接准确性的正确测试。对抗原-抗体对中相互作用的分析表明，在构建此类复合物的成对势时，应考虑界面两侧疏水斑块的不对称性。在其他一些DARS对接结果较差的复合物中也确实存在类似的不对称性。
