2026-10-14T12:24:15Z https://api.figshare.com/v2/oai

oai:figshare.com:article/32982696 2026-09-25T10:59:47Z category_1 category_4 category_915 category_15 category_19 category_21 category_873 category_734 category_931 portal_87 item_type_3 month_year_09_2026

Virtual screening of secondary metabolites from the African natural products database against <i>Plasmodium falciparum</i>: an integrated docking, MM-GBSA, and molecular dynamics study Jean Yves Takoua Bella (24391308) Gide Duriez Zantia Sogmo (24391311) Nyangono Ndongo Martin (24391314) Auguste Abouem À. Zintchem (24391317) Biophysics Biochemistry Physical Sciences not elsewhere classified Neuroscience Pharmacology Biotechnology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Information Systems not elsewhere classified Plasmodium falciparum African Natural Products Database molecular dynamics multi-target screening antimalarial drug discovery <p>An integrated pipeline combining QM ligand optimisation, docking, statistical enrichment, ADMET profiling, MM-GBSA rescoring and replicate MD simulations screened 443 secondary metabolites from the African Natural Products Database against 18 <i>P. falciparum</i> proteins. Docking validation (co-crystallized ligand RMSD 0.62–2.13 Å, median 1.35 Å) and benchmarking with chloroquine and artemisinin confirmed protocol reliability. Docking (GBVI/WSA dG ≤ −9 kcal/mol) produced 1130 hits, with class specific enrichment: flavonoids on PfAdSS, quinones on PfMyoA, terpenoids on PfDHODH. MM-GBSA rescoring of 191 priority complexes identified Stachannin A/PfDHODH (−106.50 kcal/mol) and 4-O-galloyl-gallotannin/PfDHFR-TS (−97.28 kcal/mol) as the strongest binders. Triplicate 200 ns MD simulations, extended to 1 µs for 4-O-galloyl-gallotannin/PfDHFR-TS and Jozimine A2/PfPNP, showed Jozimine A2 (IC₅₀ 1.4 nM) stably bound (Cα-RMSD 1.41 ± 0.16 Å; ligand RMSD ∼1.5 Å in two replicates, a stable alternative pose at ∼4.1 Å in the third, persistent for 1 µs) with key H-bonds to Cys208 and Tyr160. Stachannin A and 4-O-galloyl-gallotannin exhibited reproducible poses, while ceramide Liebrechtsianoside A retained occupancy but underwent tail-rotation reorganisation (ligand RMSD 13.5 ± 3.9 Å, ΔG_bind −49.5 ± 4.0 kcal/mol). PCA, free-energy landscapes and per-residue decomposition confirmed reproducibility. Four computational candidates emerge: Jozimine A2, Stachannin A, 4-O-galloyl-gallotannin and Albizia budmunchiamine alkaloids.</p> 2026-09-25T10:59:47Z Dataset Dataset 10.6084/m9.figshare.32982696.v2 https://figshare.com/articles/dataset/Virtual_screening_of_secondary_metabolites_from_the_African_natural_products_database_against_i_Plasmodium_falciparum_i_an_integrated_docking_MM-GBSA_and_molecular_dynamics_study/32982696 CC BY 4.0