Ensembling and filtering: an effective and rapid in silico multitarget drug-design strategy to identify RIPK1 and RIPK3 inhibitors

Fayaz, S M and Rajanikant, G K (2016) Ensembling and filtering: an effective and rapid in silico multitarget drug-design strategy to identify RIPK1 and RIPK3 inhibitors. Journal of Molecular Modeling, 12 (21). pp. 314-327. ISSN 1610-2940

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Official URL: http://link.springer.com/article/10.1007/s00894-01...

Abstract

Necroptosis, a programmed necrosis pathway, is witnessed in diverse human diseases and is primarily regulated by receptor-interacting serine/threonine protein kinase 1 (RIPK1) and RIPK3. Ablation or inhibition of these individual proteins, or both, has been shown to be protective in various in vitro and in vivo disease models involving necroptosis. In this study, we propose an effective and rapid virtual screening strategy to identify multitarget inhibitors of both RIPK1 and RIPK3. It involves ensemble pharmacophore-based screening (EPS) of a compound database, post-EPS filtration (PEPSF) of the ligand hits, and multiple dockings. Structurally diverse inhibitors were identified through ensemble pharmacophore features, and the speed of this process was enhanced by filtering out the compounds containing crossfeatures. The stability of these inhibitors with both of the proteins was verified by means of molecular dynamics (MD) simulation.

Item Type: Article
Uncontrolled Keywords: Ensemble pharmacophore . Ensemble docking . Dual ensemble screening (DES) . Ensemble pharmacophore-based screening (EPS) . Post-EPS filtration (PEPSF) . Dual inhibitors
Subjects: Engineering > MIT Manipal > Biotechnology
Depositing User: MIT Library
Date Deposited: 07 Nov 2016 10:52
Last Modified: 07 Nov 2016 10:52
URI: http://eprints.manipal.edu/id/eprint/147481

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