Computational study on natural compounds inhibitor of c-Myc
| Autor: | Weihang Li, Junan Ren, Liyan Zhao, Xinhui Wang, Junliang Ge, Yuhao Huangfu, Bo Wu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
CYP2D6
Protein Conformation Drug Evaluation Preclinical Antineoplastic Agents c-Myc inhibitor Computational biology Molecular Dynamics Simulation Molecular Docking Simulation Proto-Oncogene Proteins c-myc Small Molecule Libraries Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Quality Improvement Study Humans Structure–activity relationship Medicine 030212 general & internal medicine Binding site ADME Virtual screening Binding Sites business.industry General Medicine virtual screening 030220 oncology & carcinogenesis business Research Article Discovery Studio |
| Zdroj: | Medicine |
| ISSN: | 1536-5964 0025-7974 |
| DOI: | 10.1097/md.0000000000023342 |
| Popis: | To screen and identify ideal leading compounds from a drug library (ZINC15 database) with potential inhibition effect against c-Myc to contribute to medication design and development. A series of computer-aided virtual screening techniques were performed to identify potential inhibitors of c-Myc. LibDock from the software Discovery Studio was used to do a structure-based screening after ADME (absorption, distribution, metabolism, excretion) and toxicity prediction. Molecular docking was utilized to show the binding affinity and potential mechanism between ligands and c-Myc. Stability of the ligand-receptor complex was analyzed by molecular dynamic simulation at the end of the research. Compounds with more interactive energy which are confirmed to be the potential inhibitors for c-Myc were identified from the ZINC15 databases. Additionally, those compounds are also anticipated with fewer ames mutagenicity, rodent carcinogenicity, nondevelopmental toxic potential, and tolerant with cytochrome p450 2D6(CYP2D6). Dynamic simulation analysis also revealed that the very compounds had more favorable potential energy compared with 10058-F4(ZINC12406714). Furthermore, we prove that those compounds are stable and can exist in natural conditions. This study demonstrates that the compounds are potential therapeutic inhibitors for c-Myc. These compounds are safe and stable for drug candidates and may play a critical role in c-Myc inhibitor development. |
| Databáze: | OpenAIRE |
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