Physik-Department T38, Technische Universität München, James-Franck-Strasse, D-85748 Garching, Germany.
Curr Med Chem. 2010;17(15):1550-62. doi: 10.2174/092986710790979944.
The majority of biological processes involve the association of proteins or binding of other ligands to proteins. The accurate prediction of putative binding sites on the protein surface can be very helpful for rational drug design on target proteins of medical relevance, for predicting the geometry of protein-protein as well as protein-ligand complexes and for evaluating the tendency of proteins to aggregate or oligomerize. A variety of computational methods to rapidly predict protein-protein binding interfaces or binding sites for small drug-like molecules have been developed in recent years. The principles of methods available for protein interface and pocket detection are summarized, including approaches based on sequence conservation, as well as geometric and physicochemical surface properties. The performance of several Webaccessible methods for ligand binding site prediction has been compared using protein structures in bound and unbound conformation and homology modeled proteins. All methods tested gave very promising predictions even on unbound and homology modeled protein structures, thus indicating that current methods are robust in relation to modest conformational changes associated with the ligand binding process.
大多数生物过程都涉及蛋白质的结合或其他配体与蛋白质的结合。准确预测蛋白质表面上的潜在结合位点对于合理设计与医学相关的靶蛋白药物、预测蛋白质-蛋白质以及蛋白质-配体复合物的几何形状以及评估蛋白质聚集或寡聚化的趋势非常有帮助。近年来，已经开发出了多种用于快速预测蛋白质-蛋白质结合界面或小分子药物结合位点的计算方法。本文总结了用于蛋白质界面和口袋检测的方法原理，包括基于序列保守性的方法以及基于几何形状和物理化学表面特性的方法。使用结合和未结合构象的蛋白质结构以及同源建模蛋白质比较了几种可用于配体结合位点预测的 Web 方法的性能。所有测试的方法即使在未结合和同源建模的蛋白质结构上也给出了非常有前途的预测，这表明当前的方法在与配体结合过程相关的适度构象变化方面具有稳健性。
