Study summary · research use only
The role of ETFS amino acids on the stability and inhibition of p53-MDM2 complex of anticancer p53-derivatives peptides: Density functional theory and molecular docking studies
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This computational study (species not specified; a density functional theory and molecular docking analysis, not an animal or human trial) examined ETFS amino acids and p53-derived peptides targeting the p53-MDM2 complex, using DFT-BHandHLYP level chemical descriptors in aqueous solution and molecular docking. The authors report that amino acids E17, T18, and S20 increased intermolecular hydrogen bonding and structural stability, while F19, W23, and V25 were associated with enhanced alpha-helix formation, and that backbone hydrogen bonds stabilized the α-helices of PNC-27, PNC-27-B, and PNC-28 more than side-chain hydrogen bonds. Docking results indicated the PNC27B-MDM2, PNC28B-MDM2, PNC27-MDM2, and PNC28A-MDM2 complexes had the strongest binding energies, leading the authors to describe PNC-28B, PNC-27B, and PNC-28A as peptides that could inhibit MDM2 binding to p53 in this modeling study.
Abstract
Cancer is one of the leading causes of mortality in the world. Despite the existence of diverse antineoplastic treatments, these do not possess the expected efficacy in many cases. Knowledge of the molecular mechanisms involved in tumor processes allows the identification of a greater number of therapeutic targets employed in the study of new anticancer drugs. In the last decades, peptide-based therapy design using computational chemistry has gained importance in the field of oncology therapeutics. This work aims to evaluate the electronic structure, physicochemical properties, stability, and inhibition of ETFS amino acids and peptides derived from the p53-MDM2 binding domain with action in cancer cells; by means of chemical descriptors at the DFT-BHandHLYP level in an aqueous solution, and its intermolecular interactions through molecular docking studies. The results show that The ETFS fragment plays a critical role in the intermolecular interactions. Thus, the amino acids E17, T18 and S20 increase intermolecular interactions through hydrogen bonds and enhance structural stability. F19, W23 and V25 enhance the formation of the alpha-helix. The hydrogen bonds formed by the backbone atoms for PNC-27, PNC-27-B and PNC-28 stabilize the α-helices more than hydrogen bonds formed by the side chains atoms. Also, molecular docking indicated that the PNC27B-MDM2, PNC28B-MDM2, PNC27-MDM2 and PNC28A-MDM2 complexes show the best binding energy. Therefore, DFT and molecular docking studies showed that the proposed peptides: PNC-28B, PNC-27B and PNC-28A could inhibit the binding of MDM2 to the p53 protein, decreasing the translocation and degradation of p53 native protein.
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