Molecular dynamics simulations assisted investigation of phytochemicals as potential lead candidates against anti-apoptotic Bcl-B protein

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 15

Published: Dec. 18, 2023

Due to the multifarious nature of cancer, finding a single definitive cure for this dreadful disease remains an elusive challenge. The dysregulation apoptotic pathway or programmed cell death, governed by Bcl-2 family proteins plays crucial role in cancer development and progression. Bcl-B stands out as unique anti-apoptotic protein from that selectively binds Bax which inhibits its pro-apoptotic function. Although several inhibitors are reported proteins, no specific available against protein. This study aims address research gap using virtual screening in-house library phytochemicals seven anti-cancer medicinal plants identify lead molecules Through pharmacokinetic analysis molecular docking studies, we identified three candidates (Enterolactone, Piperine, Protopine) based on appreciable drug-likeliness, ADME properties, binding affinity values. also exhibited interactions with critical amino acid residues cleft, highlighting their potential candidates. Finally, dynamics simulations MM/PBSA free energy revealed Enterolactone (CID_114739) Piperine (CID_638024) were par Obatoclax (CID_11404337), is known inhibitor proteins.Communicated Ramaswamy H. Sarma.

Language: Английский

Identification of Antiviral Drug Candidates Against Monkeypox DNA Polymerase and Profilin-like Protein A42R Utilizing anIn-SilicoApproach

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

ABSTRACT Monkeypox virus (MPXV) is emerging as a major concern in the field of infectious diseases. Current treatments are limited, highlighting need for new therapeutic options. The use computational methods, such molecular docking and dynamic (MD) simulations, valuable approach identifying potential compounds that can target specific proteins virus, like DNA polymerase profilin-like protein A42R this case, with aim controlling disease. Our study focused on screening various libraries predicted binding to MPXV DPol proteins, top-performing molecules identified based their scores. Among these, Dorsilurin K Mangostin complex DPol, whereas [2-oxo-2-[3-(3,4,5,6-tetrahydro-2H-azepin-7-ylsulfamoyl)anilino]ethyl] 3,5-dimethylbenzoate N-[4-[2-[4-(4-methylphenyl)sulfonylpiperazin-1-yl]-2-oxoethoxy]phenyl]furan-2-carboxamide stand out notably high scores, suggesting they may have good affinity respectively. MD simulations confirmed stability these ligand-protein complexes followed by evaluation ADMET oral bioavailability analysis. However, it important methods suggest promising candidates, vitro eventually vivo studies essential validate candidates. Further will provide insights into efficacy, safety, side effects. In conclusion, offers avenues developing Monkeypox. If prove effective further studies, could be significant breakthrough managing zoonotic

Language: Английский