Molecular Docking and Molecular Dynamics Study of Propolis Compounds of Sulabiroin-A, Sulabiroin-B, and Broussoflavonol F Toward Tuberculosis 3PTY Target Protein.

Abstract

Molecular docking and molecular dynamics simulations were conducted to assess propolis compounds of sulabiroin-A, sulabiroin-B, and broussoflavonol F as tuberculosis (TB) inhibitors with rifampicin as the control ligand. TB remains a significant world health concern, requiring the development of new drug candidates to address more drug-resistant variants. The target protein chosen was 3PTY. The molecular docking simulation showed that sulabiroin-A, sulabiroin-B, and broussoflavonol F docking scores are comparable to rifampicin, with the order of docking score from least favorable to more favorable is sulabiroin-B< sulabiroin-A< rifampicin< broussoflavonol F (-3.397, -3.449, -5.256, -5.961). Molecular dynamics simulations also demonstrated that sulabiroin-B exhibited stable interactions with the target protein, comparable to rifampicin, while sulabiroin-A and broussoflavonol F demonstrated increased fluctuation, suggesting possible instability. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) study verified that all three drugs possess advantageous pharmacokinetic characteristics, with broussoflavonol F exhibiting the most favorable safety and tolerability profile. According to these findings, sulabiroin-B is recognized as the most promising candidate for TB treatment owing to its enhanced stability in molecular dynamics simulations, although broussoflavonol F and sulabiroin-A exhibit intermediate promise. Additional experimental validation is advised to verify their therapeutic efficacy.