Floquet Nicolas, Marechal Jean-Didier, Badet-Denisot Marie-Ange, Robert Charles H, Dauchez Manuel, Perahia David
Institut de Chimie des Substances Naturelles, ICSN, CNRS UPR-2301, Bat. 27 Avenue de la Terrasse, 91198 Gif sur Yvette, France.
FEBS Lett. 2006 Oct 2;580(22):5130-6. doi: 10.1016/j.febslet.2006.08.037. Epub 2006 Sep 1.
We demonstrate the utility of normal mode analysis in correctly predicting the binding modes of inhibitors in the active sites of matrix metalloproteinases (MMPs). We show the accuracy in predicting the positions of MMP-3 inhibitors is strongly dependent on which structure is used as the target, especially when it has been energy minimized. This dependency can be overcome by using intermediate structures generated along one of the normal modes previously calculated for a given target. These results may be of prime importance for further in silico drug discovery.
我们证明了正常模式分析在正确预测基质金属蛋白酶（MMPs）活性位点中抑制剂结合模式方面的实用性。我们表明，预测MMP - 3抑制剂位置的准确性很大程度上取决于用作目标的结构，特别是当该结构已经进行了能量最小化处理时。通过使用沿先前为给定目标计算的正常模式之一生成的中间结构，可以克服这种依赖性。这些结果对于进一步的计算机辅助药物发现可能至关重要。
