Abstract
The use of multiple target conformers has been applied successfully in virtual screening campaigns; however, a study on how to best combine scores for multiple targets in a hierarchic method that combines rigid and flexible docking is not available. In this study, we used a data set of 59479 compounds to screen multiple conformers of four distinct protein targets to obtain an adapted and optimized combination of an established hierarchic method that employs the programs FRED and Surflex. Our study was extended and verified by application of our protocol to ten different data sets from the directory of useful decoys (DUD). We quantitated overall method performance in ensemble docking and compared several consensus scoring methods to improve the enrichment during virtual ligand screening. We conclude that one of the methods used, which employs a consensus weighted scoring of multiple target conformers, performs consistently better than methods that do not include such consensus scoring. For optimal overall performance in ensemble docking, it is advisable to first calculate a consensus of FRED results and use this consensus as a sub-data set for Surflex screening. Furthermore, we identified an optimal method for each of the chosen targets and propose how to optimize the enrichment for any target.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
