SHAPE COMPLEMENTARITY AT PROTEIN-PROTEIN INTERFACES
SHAPE COMPLEMENTARITY AT PROTEIN-PROTEIN INTERFACES
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DOI：
10.1002/bip.360340711
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发表时间：
1994-07-01
期刊：
影响因子：
2.9
通讯作者：
NUSSINOV, R
中科院分区：
文献类型：
--
作者：
NOREL, R;LIN, SL;NUSSINOV, R
一个匹配算法，利用受体和配体蛋白分子之间的表面互补性概述。分子表面用“临界点”来表示，描述了孔和球。孔（形状函数的最大值）与旋钮（最小值）匹配。这种简单且吸引人的表面表示先前已由Connolly描述[（1986）Biopolymers，第25卷，第100页]。1229-1247]。然而，在对接方案中实现该描述的尝试是不成功的（例如，Connolly，同上）。为了降低组合的复杂性，并使执行时间负担得起的，四个关键孔/旋钮点匹配被寻求。这种方法失败了，因为一些绑定接口是相对平坦的，不具有四个临界点匹配。另一方面，较少临界点的匹配需要非常耗时的全构象（网格）空间搜索[Wang，（1991）Journal of Computational Chemistry，Vol.12，pp. 746-750]。在这里，我们表明，尽管这种方法的初始失败，在匹配算法中进行简单而直接的修改，这种表面表示效果良好。在我们尝试的16种蛋白质-蛋白质复合物中，有15种成功对接，包括两种免疫球蛋白。考虑了整个分子表面，绝对没有关于结合位点的额外信息。整个过程是完全自动化的，在输入原子坐标数据或匹配中没有人工干预。我们已经能够达到这个水平的性能与孔/旋钮表面的描述，通过使用对临界点沿着与他们的表面法线在计算的转换矩阵。这种方法的成功表明，未来的对接方法应该使用几何对接作为第一个筛选过滤器。由于基于几何学的对接方法预测正确的受体-配体结合构象，沿着预测不正确的受体-配体结合构象，因此所有溶液都需要进行能量筛选以区分它们。(C)John Wiley & Sons，Inc.
A matching algorithm using surface complementarity between receptor and ligand protein molecules is outlined. The molecular surfaces are represented by ''critical points,'' describing holes and knobs. Holes (maxima of a shape function) are matched with knobs (minima). This simple and appealing surface representation has been previously described by Connolly [(1986) Biopolymers, Vol. 25, pp. 1229-1247]. However, attempts to implement this description in a docking scheme have been unsuccessful (e.g., Connolly, ibid.). In order to decrease the combinatorial complexity, and to make the execution time affordable, four critical hole/knob point matches were sought. This approach failed since some bound interfaces are relatively flat and do not possess four critical point matches. On the other hand, matchings of fewer critical points require a very time-consuming, full conformational (grid) space search [Wang, (1991) Journal of Computational Chemistry, Vol. 12, pp. 746-750]. Here we show that despite the initial failure of this approach, with a simple and straightforward modification in the matching algorithm, this surface representation works well. Out of the 16 protein-protein complexes we have tried, 15 were successfully docked, including two immunoglobulins. The entire molecular surfaces were considered, with absolutely no additional information regarding the binding sites. The whole process is completely automated, with no manual intervention, either in the input atomic coordinate data, or in the matching. We have been able to reach this level of performance with the hole/knob surface description by using pairs of critical points along with their surface normals in the calculation of the transformation matrix. The success of this approach suggests that future docking methods should use geometric docking as the first screening filter. As a geometrically based docking methodology predicts correct, along with incorrect, receptor-ligand bound conformations, all solutions need to undergo energy screening to differentiate between them. (C) 1994 John Wiley & Sons, Inc.