In Silico Screening and Molecular Dynamics Validation of Bryophyllum Pinnatum Flavonoids as Pi3kγ Inhibitors For Rheumatoid Arthritis
Abstract
Abstract Rheumatoid arthritis (RA) is a long-term autoimmune inflammatory disorder that causes progressive joint destruction. This damage is partly due to the unusual activation of the phosphatidylinositol 3 kinase gamma (PI3Kγ) isoform in immune cells and synovial fibroblasts. In this study, a computational method that combined molecular docking, pharmacophore modelling, ADMET prediction, binding free energy calculations, AutoQSAR modelling, and 100 ns molecular dynamics (MD) simulations was used, and aimed to assess the potential of bioactive compounds from Bryophyllum pinnatum against PI3Kγ (PDB ID: 2A4Z) as a new target for treating RA. The molecular docking showed that Luteolin, Quercetin and Kaempferol could be potenial lead with docking scores of -11.044, -10.723 and − 10.553 respectively. The lead compounds were found to interact with specific amino acid residues that are important for inhibition of PI3Kγ. ADMET profiling indicated favourable drug-like qualities, meeting Lipinski's Rule of Five and having acceptable TPSA and logKp values. The MM-GBSA binding free energies ranged from − 45.07 to − 44.03 kcal/mol, suggesting stronger and more stable binding than tofacitinib's − 21.04 kcal/mol. AutoQSAR predicted pIC₅₀ values reinforced the high inhibitory potency, with luteolin showing the greatest predicted activity at 7.053. The MD simulations over 100 ns indicated conformational stability, with RMSD values primarily below 3.6 Å for the protein backbone and…
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Evidence Hub reads this as a preprint, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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