N. Jamali, Roohollah Mohseni, Mansoor Zareei, Javad Saffari-Chaleshtori
{"title":"奥美拉唑作为治疗癌症的潜在 CDK 抑制剂对 CDK 2、4 和 6 的分子对接和分子动力学效应","authors":"N. Jamali, Roohollah Mohseni, Mansoor Zareei, Javad Saffari-Chaleshtori","doi":"10.2174/0115733947274344231116113325","DOIUrl":null,"url":null,"abstract":"\n\nCyclin-dependent kinases (CDKs) are serine/threonine kinase proteins that\nregulate the cell cycle through phosphorylation and dephosphorylation. These proteins are a main\ntarget in cancer therapy. This study investigated the effect of omeprazole on CDK2, CDK4, and\nCDK6 through simulation studies.\n\n\n\nTo investigate the interaction between omeprazole and CDK2, 4, and 6, the threedimensional structure of omeprazole was obtained from PubChem, and the structures of CDK2, 4, and 6 were acquired from RCSB servers. The proteins were then simulated for 50 nanoseconds using the GROMACS 2021 platform before the docking process. Next, Autodock v.4.2.6 software was used to bind omeprazole as a ligand to these proteins, and a molecular dynamics simulation of the resulting protein-ligand complex was conducted using GROMACS after the docking process.\n\n\n\nOmeprazole exhibited a high affinity for interacting with CDK2, 4, and 6, mainly occurring\nin the ATP binding site of CDK4. However, the docking of omeprazole in the CDKs induced conformational\nchanges in their structures, which could potentially affect their function and lead to cell\ncycle arrest.\n\n\n\nOmeprazole, which is a proton pump inhibitor, can induce cell cycle arrest by interacting\nwith the ATP-binding site of CDK4. Moreover, it can also induce conformational changes in\nCDK2, CDK4, and CDK6 through high-affinity interactions with specific amino acid residues.\n","PeriodicalId":503819,"journal":{"name":"Current Cancer Therapy Reviews","volume":"82 12","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Molecular Docking and Molecular Dynamic Effects of Omeprazole on\\nCDKs 2, 4, and 6 as a Potential CDK Inhibitor in Cancer Treatment\",\"authors\":\"N. Jamali, Roohollah Mohseni, Mansoor Zareei, Javad Saffari-Chaleshtori\",\"doi\":\"10.2174/0115733947274344231116113325\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"\\n\\nCyclin-dependent kinases (CDKs) are serine/threonine kinase proteins that\\nregulate the cell cycle through phosphorylation and dephosphorylation. These proteins are a main\\ntarget in cancer therapy. This study investigated the effect of omeprazole on CDK2, CDK4, and\\nCDK6 through simulation studies.\\n\\n\\n\\nTo investigate the interaction between omeprazole and CDK2, 4, and 6, the threedimensional structure of omeprazole was obtained from PubChem, and the structures of CDK2, 4, and 6 were acquired from RCSB servers. The proteins were then simulated for 50 nanoseconds using the GROMACS 2021 platform before the docking process. Next, Autodock v.4.2.6 software was used to bind omeprazole as a ligand to these proteins, and a molecular dynamics simulation of the resulting protein-ligand complex was conducted using GROMACS after the docking process.\\n\\n\\n\\nOmeprazole exhibited a high affinity for interacting with CDK2, 4, and 6, mainly occurring\\nin the ATP binding site of CDK4. However, the docking of omeprazole in the CDKs induced conformational\\nchanges in their structures, which could potentially affect their function and lead to cell\\ncycle arrest.\\n\\n\\n\\nOmeprazole, which is a proton pump inhibitor, can induce cell cycle arrest by interacting\\nwith the ATP-binding site of CDK4. Moreover, it can also induce conformational changes in\\nCDK2, CDK4, and CDK6 through high-affinity interactions with specific amino acid residues.\\n\",\"PeriodicalId\":503819,\"journal\":{\"name\":\"Current Cancer Therapy Reviews\",\"volume\":\"82 12\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-01-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Cancer Therapy Reviews\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/0115733947274344231116113325\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Cancer Therapy Reviews","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115733947274344231116113325","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
The Molecular Docking and Molecular Dynamic Effects of Omeprazole on
CDKs 2, 4, and 6 as a Potential CDK Inhibitor in Cancer Treatment
Cyclin-dependent kinases (CDKs) are serine/threonine kinase proteins that
regulate the cell cycle through phosphorylation and dephosphorylation. These proteins are a main
target in cancer therapy. This study investigated the effect of omeprazole on CDK2, CDK4, and
CDK6 through simulation studies.
To investigate the interaction between omeprazole and CDK2, 4, and 6, the threedimensional structure of omeprazole was obtained from PubChem, and the structures of CDK2, 4, and 6 were acquired from RCSB servers. The proteins were then simulated for 50 nanoseconds using the GROMACS 2021 platform before the docking process. Next, Autodock v.4.2.6 software was used to bind omeprazole as a ligand to these proteins, and a molecular dynamics simulation of the resulting protein-ligand complex was conducted using GROMACS after the docking process.
Omeprazole exhibited a high affinity for interacting with CDK2, 4, and 6, mainly occurring
in the ATP binding site of CDK4. However, the docking of omeprazole in the CDKs induced conformational
changes in their structures, which could potentially affect their function and lead to cell
cycle arrest.
Omeprazole, which is a proton pump inhibitor, can induce cell cycle arrest by interacting
with the ATP-binding site of CDK4. Moreover, it can also induce conformational changes in
CDK2, CDK4, and CDK6 through high-affinity interactions with specific amino acid residues.