caa a22 4500 605511705 CHVBK 20210128100652.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00894-015-2855-2 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2855-2 Ensembling and filtering: an effective and rapid in silico multitarget drug-design strategy to identify RIPK1 and RIPK3 inhibitors [Elektronische Daten] [S. Fayaz, G. Rajanikant] 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 cross-features. The stability of these inhibitors with both of the proteins was verified by means of molecular dynamics (MD) simulation. Graphical Abstract A generalized workflow employed in this study. Subsequent utilization of EPS and PEPSF might lead to reduced computational time and load. Springer-Verlag Berlin Heidelberg, 2015 Ensemble pharmacophore nationallicence Ensemble docking nationallicence Dual ensemble screening (DES) nationallicence Ensemble pharmacophore-based screening (EPS) nationallicence Post-EPS filtration (PEPSF) nationallicence Dual inhibitors nationallicence Fayaz S. School of Biotechnology, National Institute of Technology Calicut, 673601, Calicut, India aut Rajanikant G. School of Biotechnology, National Institute of Technology Calicut, 673601, Calicut, India aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/12(2015-12-01), 1-13 1610-2940 21:12<1 2015 21 894 https://doi.org/10.1007/s00894-015-2855-2 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/s00894-015-2855-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fayaz S. School of Biotechnology, National Institute of Technology Calicut, 673601, Calicut, India aut NATIONALLICENCE 700 1- Rajanikant G. School of Biotechnology, National Institute of Technology Calicut, 673601, Calicut, India aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/12(2015-12-01), 1-13 1610-2940 21:12<1 2015 21 894