Shape-Based Descriptors for Efficient Structure-Based Fragment Growing.

Journal of Chemical Information and Modeling
Patrick PennerMatthias Rarey

Abstract

Structure-based fragment growing is one of the key techniques in fragment-based drug design. Fragment growing is commonly practiced based on structural and biophysical data. Computational workflows are employed to predict which fragment elaborations could lead to high-affinity binders. Several such workflows exist but many are designed to be long running noninteractive systems. Shape-based descriptors have been proven to be fast and perform well at virtual-screening tasks. They could, therefore, be applied to the fragment-growing problem to enable an interactive fragment-growing workflow. In this work, we describe and analyze the use of specific shape-based directional descriptors for the task of fragment growing. The performance of these descriptors that we call ray volume matrices (RVMs) is evaluated on two data sets containing protein-ligand complexes. While the first set focuses on self-growing, the second measures practical performance in a cross-growing scenario. The runtime of screenings using RVMs as well as their robustness to three dimensional perturbations is also investigated. Overall, it can be shown that RVMs are useful to prefilter fragment candidates. For up to 84% of the 3299 generated self-growing cases and fo...Continue Reading

References

Feb 1, 1992·Journal of Computer-aided Molecular Design·H J Böhm
Aug 23, 1996·Journal of Molecular Biology·M RareyG Klebe
Jul 15, 2000·Journal of Computer-aided Molecular Design·G SchneiderP Schneider
Oct 14, 2003·Drug Discovery Today·Miles CongreveHarren Jhoti
Jan 28, 2005·Angewandte Chemie·Tobias FinkJean-Louis Reymond
Aug 17, 2005·Current Topics in Medicinal Chemistry·Ansgar SchuffenhauerEdgar Jacoby
Aug 12, 2006·ChemMedChem·Jörg Degen, Matthias Rarey
Jan 5, 2007·Journal of Medicinal Chemistry·Paul C D HawkinsAnthony Nicholls
Feb 10, 2007·Nature Reviews. Drug Discovery·Philip J Hajduk, Jonathan Greer
Feb 24, 2007·Journal of Chemical Information and Modeling·Uli Fechner, Gisbert Schneider
Apr 26, 2011·Journal of Chemical Information and Modeling·Yaxia YuanLuhua Lai
Sep 23, 2011·Journal of Chemical Information and Modeling·Angelo D FaviaAndrea Cavalli
Feb 24, 2012·PLoS Computational Biology·Markus HartenfellerGisbert Schneider
Dec 12, 2012·Journal of Chemical Information and Modeling·Laurent Hoffer, Dragos Horvath
Jan 1, 2014·Expert Opinion on Drug Discovery·Heping ZhengWladek Minor
Feb 5, 2014·Journal of Chemical Information and Modeling·Diane Joseph-McCarthyDemetri Moustakas
May 1, 2015·Nucleic Acids Research·Alexander S Rose, Peter W Hildebrand
Sep 12, 2015·Journal of Medicinal Chemistry·Nicolas ChéronEugene I Shakhnovich
Dec 19, 2015·Journal of Chemical Information and Modeling·Wolfgang GubaJérôme Hert
Jan 14, 2016·Journal of Chemical Information and Modeling·Stefan Bietz, Matthias Rarey
Jul 16, 2016·Nature Reviews. Drug Discovery·Daniel A ErlansonHarren Jhoti
Dec 17, 2016·Journal of Medicinal Chemistry·Shipra Malhotra, John Karanicolas
Feb 10, 2017·Accounts of Chemical Research·Zhihai LiuRenxiao Wang
May 13, 2017·Journal of Medicinal Chemistry·Eva NittingerMatthias Rarey
Apr 3, 2018·Biophysical Journal·Rommie E AmaroJeremy C Smith
Aug 1, 2018·European Journal of Medicinal Chemistry·Jean-Rémy Marchand, Amedeo Caflisch
Aug 10, 2018·Frontiers in Chemistry·Ashutosh Kumar, Kam Y J Zhang
Nov 28, 2018·Journal of Chemical Information and Modeling·Minyi SuRenxiao Wang
Dec 24, 2018·European Journal of Medicinal Chemistry·Kai SommerMatthias Rarey
Feb 13, 2019·Journal of Chemical Information and Modeling·Nils-Ole FriedrichMatthias Rarey
Sep 4, 2019·Journal of Chemical Information and Modeling·Marco FoscatoVidar R Jensen

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Citations

Sep 3, 2021·Acta Crystallographica. Section D, Structural Biology·Alexander MetzManfred S Weiss

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