Electrostatics in protein-protein docking
Electrostatics in protein-protein docking
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DOI：
10.1110/ps.26002
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发表时间：
2002-03-01
期刊：
影响因子：
8
通讯作者：
Eisenstein, M
中科院分区：
文献类型：
--
作者：
Heifetz, A;Katchalski-Katzir, E;Eisenstein, M
提出了一种新的几何-静电对接算法，该算法将分子表面的静电互补性与形状互补性结合起来进行测试和量化。我们将每个待对接的分子表示为复数网格，在真实的部分存储关于分子形状的信息，在虚部存储关于分子静电特性的信息。静电描述符来自分子的静电势。因此，分子的静电特征表示为正值、中性值或负值的斑块。每个分子的势仅计算一次，并存储为足以进行详尽旋转/平移扫描的势球。几何静电对接算法适用于17个系统，从未结合分子的结构开始。结果的互补性得分的几乎正确的解决方案，他们的排序的解决方案的列表中的排名，和他们的统计的唯一性方面进行比较与几何对接，包括静电互补性对接是非常重要的，特别是在对接的未结合的结构。基于我们的研究结果，我们制定了几个“好的静电对接规则”的几何静电对接程序是更成功的几何对接时，潜在的补丁是大的，当潜在的延伸远离分子表面，并突出到溶剂。相比之下，当要对接的分子周围的静电势看起来均匀时，即分子周围具有相似的符号时，推荐几何对接。
A novel geometric-electrostatic docking algorithm is presented, which tests and quantifies the electrostatic complementarity of the molecular surfaces together with the shape complementarity. We represent each molecule to be docked as a grid of complex numbers, storing information regarding the shape of the molecule in the real part and information regarding the electrostatic character of the molecule in the imaginary part. The electrostatic descriptors are derived from the electrostatic potential of the molecule. Thus, the electrostatic character of the molecule is represented as patches of positive, neutral, or negative values. The potential for each molecule is calculated only once and stored as potential spheres adequate for exhaustive rotation/translation scans. The geometric-electrostatic docking algorithm is applied to 17 systems, starting form the structures of the unbound molecules. The results-in terms of the complementarity scores of the nearly correct solutions, their ranking in the lists of sorted solutions, and their statistical uniqueness-are compared with those of geometric docking, showing that the inclusion of electrostatic complementarity in docking is very important, in particular in docking of unbound structures. Based on our results, we formulate several "good electrostatic docking rules"; The geometric-electrostatic docking procedure is more successful than geometric docking when the potential patches are large and when the potential extends away from the molecular surface and protrudes into the solvent. In contrast, geometric docking is recommended when the electrostatic potential around the molecules to be docked appears homogenous, that is, with a similar sign all around the molecule.