In Silico Effects of Thalidomide and Its Analogs on BCL-2 and BRCA1: Molecular Docking, Molecular Dynamics and Imaging Studies

Authors : Erkut Tamtürk, Serap Yalcin

Pages : 585-591

Doi:10.32708/uutfd.1762259

View : 94 | Download : 156

Publication Date : 2025-12-08

Article Type : Research Paper

Abstract :In recent years, in silico studies in molecular biology have emerged as a leading approach that accelerates experimental processes and provides economic advantages, particularly in biomedical research. As a computer-aided strategy, in silico methods contribute significantly to key areas such as the identification of novel therapeutic targets in cancer research, the visualization and analysis of molecular interactions, and the evaluation of the drug-likeness potential of chemical compounds. This study aimed to analyze the interactions of thalidomide and its analogs (lenalidomide, pomalidomide) with cancer-related proteins BCL-2 and BRCA1 using in silico approaches, in order to identify potential inhibitor candidates. Molecular docking analyses were performed using AutoDock Vina, and molecular dynamics (MD) simulations were conducted for 50 ns on the WebGro molecular dynamics computation site. System stability was assessed by RMSD, RMSF, and Rg analyses. Docking results showed that the binding energies of thalidomide, lenalidomide and pomalidomide with the BCL-2 protein were –6.8, –6.6, and –6.7 kcal/mol, respectively. For the BRCA1 protein, the binding energies were –5.3, –5.5, and –6.7 kcal/mol, respectively. MD simulations demonstrated that both free proteins and protein–ligand complexes maintained compact and stable structures throughout the simulation. The RMSD values stabilized between 0.3 and 0.5 nm, supporting the dynamic stability of the systems. Notably, thalidomide and lenalidomide enhanced the structural stability of the BCL-2 complexes. In conclusion, thalidomide derivatives exhibit moderate binding affinity and complex stability to BCL-2 and BRCA1 proteins, suggesting that these compounds can be considered as candidates for anti-cancer therapeutic agents. Future in vitro and in vivo studies are expected to further validate the biological relevance of these findings.
Keywords : BCL-2, talidomid, moleküler kenetlenme, in silico analizler, moleküler dinamik

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