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Benchmarking ensemble docking methods as a scientific outreach project

Gan, Jessie L. and Kumar, Dhruv and Chen, Cynthia and Taylor, Bryn C. and Jagger, Benjamin R. and Amaro, Rommie E. and Lee, Christopher T. (2020) Benchmarking ensemble docking methods as a scientific outreach project. . (Unpublished)

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The discovery of new drugs is a time consuming and expensive process. Methods such as virtual screening, which can filter out ineffective compounds from drug libraries prior to expensive experimental study, have become popular research topics. As the computational drug discovery community has grown, in order to benchmark the various advances in methodology, organizations such as the Drug Design Data Resource have begun hosting blinded grand challenges seeking to identify the best methods for ligand pose-prediction, ligand affinity ranking, and free energy calculations. Such open challenges offer a unique opportunity for researchers to partner with junior students (e.g., high school and undergraduate) to validate basic yet fundamental hypotheses considered to be uninteresting to domain experts. Here, we, a group of high school-aged students and their mentors, present the results of our participation in Grand Challenge 4 where we predicted ligand affinity rankings for the Cathepsin S protease, an important protein target for autoimmune diseases. To investigate the effect of incorporating receptor dynamics on ligand affinity rankings, we employed the Relaxed Complex Scheme, a molecular docking method paired with molecular dynamics-generated receptor conformations. We found that CatS is a difficult target for molecular docking and we explore some advanced methods such as distance-restrained docking to try to improve the correlation with experiments. This project has exemplified the capabilities of high school students when supported with a rigorous curriculum, and demonstrates the value of community-driven competitions for beginners in computational drug discovery.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper ItemData/Code
Gan, Jessie L.0000-0002-9053-2064
Kumar, Dhruv0000-0002-0791-0977
Chen, Cynthia0000-0003-4604-2241
Taylor, Bryn C.0000-0002-4957-5417
Jagger, Benjamin R.0000-0003-2958-3695
Amaro, Rommie E.0000-0002-9275-9553
Lee, Christopher T.0000-0002-0670-2308
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. Posted October 04, 2020. This work is supported by the National Biomedical Computation Resource NIH Grant P41-GM103426, and the National Science Foundation through The Extreme Science and Engineering Discovery Environment (XSEDE) supercomputing resources provided via Award TG-CHE060073 to R.E.A. C.T.L. is funded by a Hartwell Foundation Postdoctoral Fellowship. We thank D3R and the organizers of Grand Challenge 4 for hosting the challenge and reporting results. We would also like to acknowledge Mason V. Holst, Gaurie Gunasekaran, Gray Thoron, and Jeffery R. Wagner for their contributions to preliminary work and/or helpful discussions. Author Contributions: Conceptualization, B.C.T., B.R.J., C.T.L. and R.E.A.; Software, J.L.G., D.K., and C.C.; Investigation, J.L.G., D.K., and C.C.; Resources, B.C.T., B.R.J., C.T.L. and R.E.A.; Writing – Original Draft, J.L.G, and D.K.; Writing – Review and Editing, J.L.G, D.K., C.C., B.C.T., B.R.J., C.T.L. and R.E.A.; Visualization, J.L.G., D.K.; Supervision and Project Administration, B.C.T., B.R.J., C.T.L. and R.E.A.; Funding Acquisition, R.E.A.
Funding AgencyGrant Number
Hartwell FoundationUNSPECIFIED
Subject Keywords:Computational Biophysics; Ensemble Docking; Molecular Dynamics; Drug Discovery; Secondary Education; Undergraduate Education; Outreach Coordinators
Record Number:CaltechAUTHORS:20201006-105653492
Persistent URL:
Official Citation:Benchmarking ensemble docking methods as a scientific outreach project. Jessie L. Gan, Dhruv Kumar, Cynthia Chen, Bryn C. Taylor, Benjamin R. Jagger, Rommie E. Amaro, Christopher T. Lee. bioRxiv 2020.10.02.324343; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105837
Deposited By: Tony Diaz
Deposited On:07 Oct 2020 00:21
Last Modified:30 Oct 2020 17:54

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