Molecular docking of DS-3032B,a mouse double minute 2 enzyme antagonist with potential for oncology treatment development

作     者：Vítor Hugo Sales da Mota Fabrício Freire de Melo Breno Bittencourt de Brito Filipe Antônio França da Silva Kádima Nayara Teixeira 

作者机构：Campus ToledoUniversidade Federal do ParanáToledo 85.919-899ParanáBrazil Instituto Multidisciplinar em SaúdeUniversidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil 

出 版 物：《World Journal of Clinical Oncology》 (世界临床肿瘤学杂志（英文版）)

年 卷 期：2022年第13卷第6期

页      面：496-504页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：DS-3032B Mouse double minute 2 antagonist Molecular docking Tumor suppressor p53 

摘      要：BACKGROUND It is known that p53 suppression is an important marker of poor prognosis of cancers,especially in solid tumors of the breast,lung,stomach,and esophagus;liposarcomas,glioblastomas,and *** p53 has mouse double minute 2(MDM2)as its primary negative regulator,this molecular docking study seeks to answer the following hypotheses:Is the interaction between DS-3032B and MDM2 stable enough for this drug to be considered as a promising neoplastic inhibitor?AIM To analyze,in silico,the chemical bonds between the antagonist DS-3032B and its binding site in *** For molecular docking simulations,the file containing structures of MDM2(receptor)and the drug DS-3032B(ligand)were *** three-dimensional structure of MDM2 was obtained from Protein Data Bank,and the one for DS-3032B was obtained from PubChem *** location and dimensions of the Grid box was determined using AutoDock Tools *** this case,the dimensions of the Grid encompassed the entire *** ligand DS-3032B interacts with the MDM2 receptor in a physiological environment with pH 7.4;thus,to simulate more reliably,its interaction was made with the calculation for the prediction of its protonation state using the MarvinSketch®*** ligands,with and without the protonation,were prepared for molecular docking using the AutoDock Tools *** software detects the torsion points of the drug and calculates the angle of the *** docking simulations were performed using the tools of the AutoDock platform connected to the Vina *** analyses of the amino acid residues involved in the interactions between the receptor and the ligand as well as the twists of the ligand,atoms involved in the interactions,and type,strength,and length of the interactions were performed using the PyMol software(***/2)and Discovery Studio from BIOVIA®.RESULTS The global alignment indicated crystal structure 5SWK was more suitable for docking simulati