Protein Structural Information Analysis Team, Biological Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo 135-0064, Japan.
Protein Sci. 2011 Jan;20(1):95-106. doi: 10.1002/pro.540.
A new approach to predicting the ligand-binding sites of proteins was developed, using protein-ligand docking computation. In this method, many compounds in a random library are docked onto the whole protein surface. We assumed that the true ligand-binding site would exhibit stronger affinity to the compounds in the random library than the other sites, even if the random library did not include the ligand corresponding to the true binding site. We also assumed that the affinity of the true ligand-binding site would be correlated to the docking scores of the compounds in the random library, if the ligand-binding site was correctly predicted. We call this method the molecular-docking binding-site finding (MolSite) method. The MolSite method was applied to 89 known protein-ligand complex structures extracted from the Protein Data Bank, and it predicted the correct binding sites with about 80-99% accuracy, when only the single top-ranked site was adopted. In addition, the average docking score was weakly correlated to the experimental protein-ligand binding free energy, with a correlation coefficient of 0.44.
开发了一种新的蛋白质配体结合位点预测方法，该方法使用蛋白质-配体对接计算。在该方法中，随机库中的许多化合物被对接至整个蛋白质表面。我们假设，即使随机库中不包含与真实结合位点相对应的配体，真实配体结合位点也会与随机库中的化合物表现出更强的亲和力。我们还假设，如果配体结合位点被正确预测，那么真实配体结合位点的亲和力将与随机库中化合物的对接评分相关。我们将这种方法称为分子对接结合位点发现（MolSite）方法。MolSite 方法应用于从蛋白质数据库中提取的 89 个已知蛋白质-配体复合物结构，当仅采用单个排名最高的结合位点时，该方法预测正确的结合位点的准确率约为 80-99%。此外，平均对接评分与实验蛋白质-配体结合自由能呈弱相关性，相关系数为 0.44。
