{"title":"通过分子对接以及分子动力学、RMSD、RMSF、H-键、SASA 和 MMGBSA 方法筛选针对 SARS-CoV-2 主要蛋白酶结构的潜在抑制剂。","authors":"Aluísio Marques da Fonseca, Bernardino Joaquim Caluaco, Junilson Martinho Canjanja Madureira, Sadrack Queque Cabongo, Eduardo Menezes Gaieta, Faustino Djata, Regilany Paulo Colares, Moises Maia Neto, Carla Freire Celedonio Fernandes, Gabrielle Silva Marinho, Hélcio Silva Dos Santos, Emmanuel Silva Marinho","doi":"10.1007/s12033-023-00831-x","DOIUrl":null,"url":null,"abstract":"<p><p>Severe Acute Respiratory Syndrome caused by a coronavirus is a recent viral infection. There is no scientific evidence or clinical trials to indicate that possible therapies have demonstrated results in suspected or confirmed patients. This work aims to perform a virtual screening of 1430 ligands through molecular docking and to evaluate the possible inhibitory capacity of these drugs about the M<sup>pro</sup> protease of Covid-19. The selected drugs were registered with the FDA and available in the virtual drug library, widely used by the population. The simulation was performed using the MolAiCalD algorithm, with a Lamarckian genetic model (GA) combined with energy estimation based on rigid and flexible conformation grids. In addition, molecular dynamics studies were also performed to verify the stability of the receptor-ligand complexes formed through analyses of RMSD, RMSF, H-Bond, SASA, and MMGBSA. Compared to the binding energy of the synthetic redocking coupling (-6.8 kcal/mol/RMSD of 1.34 Å), which was considerably higher, it was then decided to analyze the parameters of only three ligands: ergotamine (-9.9 kcal/mol/RMSD of 2.0 Å), dihydroergotamine (-9.8 kcal/mol/RMSD of 1.46 Å) and olysio (-9.5 kcal/mol/RMSD of 1.5 Å). It can be stated that ergotamine showed the best interactions with the M<sup>pro</sup> protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"1919-1933"},"PeriodicalIF":2.4000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Screening of Potential Inhibitors Targeting the Main Protease Structure of SARS-CoV-2 via Molecular Docking, and Approach with Molecular Dynamics, RMSD, RMSF, H-Bond, SASA and MMGBSA.\",\"authors\":\"Aluísio Marques da Fonseca, Bernardino Joaquim Caluaco, Junilson Martinho Canjanja Madureira, Sadrack Queque Cabongo, Eduardo Menezes Gaieta, Faustino Djata, Regilany Paulo Colares, Moises Maia Neto, Carla Freire Celedonio Fernandes, Gabrielle Silva Marinho, Hélcio Silva Dos Santos, Emmanuel Silva Marinho\",\"doi\":\"10.1007/s12033-023-00831-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Severe Acute Respiratory Syndrome caused by a coronavirus is a recent viral infection. There is no scientific evidence or clinical trials to indicate that possible therapies have demonstrated results in suspected or confirmed patients. This work aims to perform a virtual screening of 1430 ligands through molecular docking and to evaluate the possible inhibitory capacity of these drugs about the M<sup>pro</sup> protease of Covid-19. The selected drugs were registered with the FDA and available in the virtual drug library, widely used by the population. The simulation was performed using the MolAiCalD algorithm, with a Lamarckian genetic model (GA) combined with energy estimation based on rigid and flexible conformation grids. In addition, molecular dynamics studies were also performed to verify the stability of the receptor-ligand complexes formed through analyses of RMSD, RMSF, H-Bond, SASA, and MMGBSA. Compared to the binding energy of the synthetic redocking coupling (-6.8 kcal/mol/RMSD of 1.34 Å), which was considerably higher, it was then decided to analyze the parameters of only three ligands: ergotamine (-9.9 kcal/mol/RMSD of 2.0 Å), dihydroergotamine (-9.8 kcal/mol/RMSD of 1.46 Å) and olysio (-9.5 kcal/mol/RMSD of 1.5 Å). It can be stated that ergotamine showed the best interactions with the M<sup>pro</sup> protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19.</p>\",\"PeriodicalId\":18865,\"journal\":{\"name\":\"Molecular Biotechnology\",\"volume\":\" \",\"pages\":\"1919-1933\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Biotechnology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12033-023-00831-x\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/7/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Biotechnology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12033-023-00831-x","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/7/25 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Screening of Potential Inhibitors Targeting the Main Protease Structure of SARS-CoV-2 via Molecular Docking, and Approach with Molecular Dynamics, RMSD, RMSF, H-Bond, SASA and MMGBSA.
Severe Acute Respiratory Syndrome caused by a coronavirus is a recent viral infection. There is no scientific evidence or clinical trials to indicate that possible therapies have demonstrated results in suspected or confirmed patients. This work aims to perform a virtual screening of 1430 ligands through molecular docking and to evaluate the possible inhibitory capacity of these drugs about the Mpro protease of Covid-19. The selected drugs were registered with the FDA and available in the virtual drug library, widely used by the population. The simulation was performed using the MolAiCalD algorithm, with a Lamarckian genetic model (GA) combined with energy estimation based on rigid and flexible conformation grids. In addition, molecular dynamics studies were also performed to verify the stability of the receptor-ligand complexes formed through analyses of RMSD, RMSF, H-Bond, SASA, and MMGBSA. Compared to the binding energy of the synthetic redocking coupling (-6.8 kcal/mol/RMSD of 1.34 Å), which was considerably higher, it was then decided to analyze the parameters of only three ligands: ergotamine (-9.9 kcal/mol/RMSD of 2.0 Å), dihydroergotamine (-9.8 kcal/mol/RMSD of 1.46 Å) and olysio (-9.5 kcal/mol/RMSD of 1.5 Å). It can be stated that ergotamine showed the best interactions with the Mpro protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19.
期刊介绍:
Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.