Ha S, Andreani R, Robbins A, Muegge I
Bayer Research Center, West Haven, CT 06516, USA.
J Comput Aided Mol Des. 2000 Jul;14(5):435-48. doi: 10.1023/a:1008137707965.
An increasing number of docking/scoring programs are available that use different sampling and scoring algorithms. A reliable scoring function is the crucial element of such approaches. Comparative studies are needed to evaluate their current capabilities. DOCK4 with force field and PMF scoring as well as FlexX were used to evaluate the predictive power of these docking/scoring approaches to identify the correct binding mode of 61 MMP-3 inhibitors in a crystal structure of stromelysin and also to rank them according to their different binding affinities. It was found that DOCK4/PMF scoring performs significantly better than FlexX and DOCK4/FF in both ranking ligands and predicting their binding modes. Most notably, DOCK4/PMF was the only scoring/docking approach that found a significant correlation between binding affinity and predicted score of the docked inhibitors. However, comparing only those cases where the correct binding mode was identified (scoring highest among sampled poses), FlexX showed the best 'fine tuning' (lowest rmsd) in predicted binding modes. The results suggest that not so much the sampling procedure but rather the scoring function is the crucial element of a docking program.
现在有越来越多的对接/评分程序，它们使用不同的采样和评分算法。可靠的评分函数是这些方法的关键要素。需要进行比较研究来评估它们当前的能力。使用带有力场和PMF评分的DOCK4以及FlexX来评估这些对接/评分方法的预测能力，以确定61种基质金属蛋白酶-3抑制剂在基质溶解素晶体结构中的正确结合模式，并根据它们不同的结合亲和力对它们进行排序。结果发现，在对配体进行排序和预测其结合模式方面，DOCK4/PMF评分的表现明显优于FlexX和DOCK4/FF。最值得注意的是，DOCK4/PMF是唯一一种在对接抑制剂的结合亲和力和预测分数之间发现显著相关性的评分/对接方法。然而，仅比较那些确定了正确结合模式（在采样构象中得分最高）的情况时，FlexX在预测结合模式方面显示出最佳的“微调”（最低均方根偏差）。结果表明，对接程序的关键要素与其说是采样过程，不如说是评分函数。
