title: An Integrated In Silico Method to Discover Novel Rock1 Inhibitors: Multi- Complex-Based Pharmacophore, Molecular Dynamics Simulation and Hybrid Protocol Virtual Screening.
abstract: Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is an important regulator of focal adhesion, actomyosin contraction and cell motility. In this manuscript, a combination of the multi-complex-based pharmacophore (MCBP), molecular dynamics simulation and a hybrid protocol of a virtual screening method, comprised of multipharmacophore- based virtual screening (PBVS) and ensemble docking-based virtual screening (DBVS) methods were used for retrieving novel ROCK1 inhibitors from the natural products database embedded in the ZINC database. Ten hit compounds were selected from the hit compounds, and five compounds were tested experimentally. Thus, these results may provide valuable information for further discovery of more novel ROCK1 inhibitors.
authors.forename: Haining
authors.initials: H
authors.lastname: Chen
authors.forename: Sijia
authors.initials: S
authors.lastname: Li
authors.forename: Yajiao
authors.initials: Y
authors.lastname: Hu
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Jiang
authors.forename: Rongsheng
authors.initials: R
authors.lastname: Tong
authors.forename: Zhihe
authors.initials: Z
authors.lastname: Zang
authors.affiliation: Department Gastrointestinal Surgery, Department of Anesthesiology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. lulu.cai@hotmail.com.
authors.forename: Lulu
authors.initials: L
authors.lastname: Cai
mesh_terms: D001665:Binding Sites; D001681:Biological Assay; D003198:Computer Simulation; D030562:Databases, Protein; D055808:Drug Discovery / Q000379:methods*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D056004:Molecular Dynamics Simulation; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases