title: Improving protein-ligand docking with flexible interfacial water molecules using SWRosettaLigand.
abstract: Computational protein-ligand docking is of great importance in drug discovery and design. Conformational changes greatly affect the results of protein-ligand docking, especially when water molecules take part in mediating protein ligand interactions or when large conformational changes are observed in the receptor backbone interface. We have developed an improved protocol, SWRosettaLigand, based on the RosettaLigand protocol. This approach incorporates the flexibility of interfacial water molecules and modeling of the interface of the receptor into the original RosettaLigand. In a coarse sampling step, SWRosettaLigand pre-optimizes the initial position of the water molecules, docks the ligand to the receptor with explicit water molecules, and minimizes the predicted structure with water molecules. The receptor backbone interface is treated as a loop and perturbed and refined by kinematic closure, or cyclic coordinate descent algorithm, with the presence of the ligand. In two cross-docking test sets, it was identified that for 8 out of 14, and 16 out of 22, test instances, the top-ranked structures by SWRosettaLigand achieved better accuracy than other protocols.
authors.affiliation: School of Computer Science and Technology, Soochow University, P.O.Box 158, 1 Shizi Street, Suzhou, Jiangsu, 215006, China.
authors.forename: Linqing
authors.initials: L
authors.lastname: Li
authors.affiliation: Wujiang Rural Commercial Bank, Suzhou, Jiangsu, 215006, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Computer Science and Technology, Soochow University, P.O.Box 158, 1 Shizi Street, Suzhou, Jiangsu, 215006, China. qiang@suda.edu.cn.|Jiangsu Provincial Key Lab for Information Processing Technologies, Suzhou, China. qiang@suda.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lü
mesh_terms: D000465:Algorithms; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011506:Proteins / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D008024:Ligands; D011506:Proteins; D014867:Water
keywords: Flexible receptor backbone interface; Flexible water molecules; MD simulations; Protein-ligand docking