Virtual screening using a conformationally flexible target protein: models for ligand binding to p38α MAPK.
作者： Natalie B. Vinh , Jamie S. Simpson , Peter J. Scammells , David K. Chalmers
DOI: 10.1007/S10822-012-9569-7
关键词:
摘要: We have used virtual screening to develop models for the binding of aryl substituted heterocycles p38α MAPK. Virtual was conducted on a number MAPK crystal structures using library 46 known inhibitors containing heterocyclic core by pyridine and fluorophenyl rings (structurally related SB203580) set decoy compounds. Multiple protonation states tautomers active compounds were considered. Each docking model evaluated receiver operating characteristic (ROC) curves enrichment factors. The two best performing single found be 1BL7 2EWA, with factors 14.1 13.0 at 2 % screen respectively. Ensembles up four receptors similar conformations generated, generally giving good or very performances high ROC AUCs enrichment. 1BL7-2EWA ensemble able outperform each its constituent gave 17.3, 12.0, 8.0 2, 5 10 respectively, screen. A AUC 0.94 obtained this ensemble. This method may applied other proteins where there are large inhibitor classes different site conformations.
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