Docking molecular de compostos bioativos contra as bactérias do complexo vermelho para periodontite

Abstract

Dental calculus results from the calcification of dental plaque and, in its most aggressive form, is associated with red complex bacteria such as P. gingivalis, T. denticola, and T. forsythia. However, therapeutic options remain limited, particularly with regard to the use of bioactive compounds as alternative treatments. In this context, the present study aims to investigate the main virulence proteins of red complex bacteria and to use them to identify potential natural inhibitors capable of interfering with pathogenicity mechanisms associated with periodontal disease through in silico approaches.To this end, we initially conducted a literature review to identify the major virulence proteins, followed by the adoption of a multitarget computational docking strategy against structural targets using a natural products ligand library (COCONUT). The virulence proteins identified in the literature were Kgp for P. gingivalis, cystalisin for T. denticola, and karilysin for T. forsythia. For docking, 57,476 compounds were used, with the removal of 844 duplicates and 32,607 similar compounds based on Morgan fingerprints (Tanimoto < 0.7; leader clustering), resulting in 23,771 ligands after conversion to (.pdbqt). Docking results at a 5.0 Å cutoff showed high site occupancy for cystalisin (84.17%) and karilysin (97.98%), but very low occupancy for Kgp (8.43%), which may reflect geometric and physicochemical differences in the sampled cavities. In the multitarget selection, 296 compounds met the strict consensus criteria (3/3 site occupancy) and were ranked by mean binding energy (E_mean); the strict Top 80 ranged from approximately −10.65 to −9.34 kcal/mol. Molecular docking screening using compounds from the COCONUT database identified N-benzyl-3-[(3S)-2,5-dioxo-3,4-dihydro-1H-1,4-benzodiazepin-3- yl]-N-methylpropanamide as the most promising multitarget candidate, simultaneously meeting the criteria for catalytic site occupancy, structural consistency, and binding energy (≤ −7.0 kcal/mol) across all three targets.