caa a22 4500 605513775 CHVBK 20210128100701.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00894-015-2834-7 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2834-7 Improving protein-ligand docking with flexible interfacial water molecules using SWRosettaLigand [Elektronische Daten] [Linqing Li, Weiwei Xu, Qiang Lü] 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. Springer-Verlag Berlin Heidelberg, 2015 Protein-ligand docking nationallicence Flexible water molecules nationallicence Flexible receptor backbone interface nationallicence MD simulations nationallicence Li Linqing School of Computer Science and Technology, Soochow University, P.O.Box 158, 1 Shizi Street, 215006, Suzhou, Jiangsu, China aut Xu Weiwei Wujiang Rural Commercial Bank, 215006, Suzhou, Jiangsu, China aut Lü Qiang School of Computer Science and Technology, Soochow University, P.O.Box 158, 1 Shizi Street, 215006, Suzhou, Jiangsu, China aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/11(2015-11-01), 1-13 1610-2940 21:11<1 2015 21 894 https://doi.org/10.1007/s00894-015-2834-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2834-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Linqing School of Computer Science and Technology, Soochow University, P.O.Box 158, 1 Shizi Street, 215006, Suzhou, Jiangsu, China aut NATIONALLICENCE 700 1- Xu Weiwei Wujiang Rural Commercial Bank, 215006, Suzhou, Jiangsu, China aut NATIONALLICENCE 700 1- Lü Qiang School of Computer Science and Technology, Soochow University, P.O.Box 158, 1 Shizi Street, 215006, Suzhou, Jiangsu, China aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/11(2015-11-01), 1-13 1610-2940 21:11<1 2015 21 894