ESTUDO DE DOCKING MOLECULAR DAS INTERAÇÕES ENTRE BERBERINA E CICLINA D1

• DOI: https://doi.org/10.22533/at.ed.6191225020112

• Palavras-chave: Bioprospecção; Pesquisa e desenvolvimento de fármacos; Bioinformática; Neoplasias malignas gastrointestinais.

• Keywords: Bioprospecting; Drug research and development; Bioinformatics; Gastrointestinal malignant neoplasms.

• Abstract: Colorectal cancer is one of the most common malignancies worldwide, with cell cycle dysregulation playing a central role in its pathogenesis. Overexpression of cyclin D1, which forms activating complexes with cyclin-dependent kinase 4/6 (CDK4/6) to promote the G1/S transition, has emerged as a promising therapeutic target. In this context, berberine (an isoquinoline alkaloid with proven antiproliferative activity) appears as a promising molecule for anticancer studies. Therefore, the objective was to evaluate the interactions between berberine and cyclin D1 through in silico studies. Modeling of human cyclin D1 was performed in SWISS-MODEL. Model refinement was performed in GalaxyRefine and stereochemical validation was performed in PROCHECK. The ligands (berberine and fascaplysin) were obtained from PubChem. Molecular docking was performed in AutoDock 4.2. The prediction of the CDK4/6 binding site was performed at GHECOM. As a result, the protein structure with excellent quality (96.7% residues in favorable regions) was obtained. The intermolecular interactions demonstrated affinity of the ligands with amino acids of the CDK4/6 binding site of cyclin D1 (binding energy: -6.81 to -5.9 kcal/mol for berberine and (-7.88 to -7.27 kcal/mol for fascaplysin). Thus, it is concluded that berberine presented a potential inhibitory effect by competition on cyclin D1, which can cause cell cycle arrest in G1/S, which makes this alkaloid a promising molecule for experimental studies to validate or discard this application.