title: Statistical analysis of EGFR structures' performance in virtual screening.
abstract: In this work the ability of EGFR structures to distinguish true inhibitors from decoys in docking and MM-PBSA is assessed by statistical procedures. The docking performance depends critically on the receptor conformation and bound state. The enrichment of known inhibitors is well correlated with the difference between EGFR structures rather than the bound-ligand property. The optimal structures for virtual screening can be selected based purely on the complex information. And the mixed combination of distinct EGFR conformations is recommended for ensemble docking. In MM-PBSA, a variety of EGFR structures have identically good performance in the scoring and ranking of known inhibitors, indicating that the choice of the receptor structure has little effect on the screening.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA. yanli0208@hi.umn.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA. zgdong@hi.umn.edu.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D014584:User-Computer Interface
chemical_list: D008024:Ligands; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR conformation; Enrichment; MM-PBSA; Molecular docking; Receptor flexibility