癌症是世界上主要的死亡原因之一。尽管存在各种抗肿瘤治疗方法，但在许多情况下，这些方法并没有达到预期的疗效。了解肿瘤过程中的分子机制可以确定更多治疗靶点，用于研究新的抗癌药物。在过去几十年中，基于多肽的治疗设计在计算化学领域中在肿瘤学治疗中变得越来越重要。本研究旨在通过DFT-BHandHLYP水溶液中的化学描述符评估p53-MDM2结合域衍生的ETFS氨基酸和多肽的电子结构、物理化学性质、稳定性和抑制作用，并通过分子对接研究其分子间相互作用。结果表明，ETFS片段在分子间相互作用中起到关键作用。因此，氨基酸E17、T18和S20通过氢键增加分子间相互作用并增强结构稳定性。F19、W23和V25增强α螺旋的形成。PNC-27、PNC-27-B和PNC-28的骨架原子所形成的氢键比侧链原子所形成的氢键更能稳定α螺旋。此外，分子对接研究表明，PNC27B-MDM2、PNC28B-MDM2、PNC27-MDM2和PNC28A-MDM2复合物具有最佳的结合能。因此，DFT和分子对接研究表明，所提出的多肽：PNC-28B、PNC-27B和PNC-28A可抑制MDM2与p53蛋白的结合，降低p53天然蛋白的转位和降解。版权所有©2023 Elsevier Inc.发表。

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.Copyright © 2023. Published by Elsevier Inc.