Chemistry Division, Naval Research Laboratory, Washington, D.C. 20375-5342, USA.
J Am Chem Soc. 2011 Jul 20;133(28):10740-3. doi: 10.1021/ja203929x. Epub 2011 Jun 23.
Simulated annealing of chemical potential located the highest affinity positions of eight organic probes and water on eight static structures of hen egg white lysozyme (HEWL) in various conformational states. In all HELW conformations, a diverse set of organic probes clustered in the known binding site (hot spot). Fragment clusters at other locations were excluded by tightly-bound waters so that only the hot-spot cluster remained in each case. The location of the hot spot was correctly predicted irrespective of the protein conformation and without accounting for protein flexibility during the simulations. Any one of the static structures could have been used to locate the hot spot. A site on a protein where a diversity of organic probes is calculated to cluster, but where water specifically does not bind, identifies a potential small-molecule binding site or protein-protein interaction hot spot.
化学势模拟退火定位了八个有机探针和水在不同构象状态的鸡卵清溶菌酶（HEWL）八个静态结构上的最高亲和力位置。在所有 HEWL 构象中，一组不同的有机探针聚集在已知的结合位点（热点）。紧密结合的水排除了其他位置的片段簇，因此在每种情况下仅保留热点簇。热点的位置是正确预测的，而不考虑蛋白质构象，并且在模拟过程中不考虑蛋白质灵活性。任何一个静态结构都可以用来定位热点。在蛋白质上，计算出多种有机探针聚集的位置，但水特异性不结合的位置，确定了潜在的小分子结合位点或蛋白质-蛋白质相互作用热点。
