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10.1039/d0nr07833f http://scihub22266oqcxt.onion/10.1039/d0nr07833f 33900318!ä!33900318 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nanoscale 2021 ; 13 (17): 8313-8332 Nephropedia Template TP {{tp|p=33900318|t=2021. Inhibition mechanism and hot-spot prediction of nine potential drugs for SARS-CoV-2 M(pro) by large-scale molecular dynamic simulations combined with accurate binding free energy calculations |pdf=|usr=}}{{33900318}} gab.com Text Inhibition mechanism and hot-spot prediction of nine potential drugs for SARS-CoV-2 M(pro) by large-scale molecular dynamic simulations combined with accurate binding free energy calculations JO: Nanoscale http://www.kidney.de/pget.php?&tw=1&pmid=33900318 #FOAvip Coronavirus disease 2019 (COVID-19), which is caused by a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading around the world. However, a universally effective treatment regimen has not been developed to date. The main protease (M(pro)), a key enzyme of SARS-CoV-2, plays a crucial role in the replication and transcription of this virus in cells and has become the ideal target for rational antiviral drug design. In this study, we performed molecular dynamics simulations three times for these complexes of M(pro) (monomeric and dimeric) and nine potential drugs that have a certain effect on the treatment of COVID-19 to explore their binding mechanism. In addition, a total of 12 methods for calculating binding free energy were employed to determine the optimal drug. Ritonavir, Arbidol, and Chloroquine consistently showed an outstanding binding ability to monomeric M(pro) under various methods. Ritonavir, Arbidol, and Saquinavir presented the best performance when binding to a dimer, which was independent of the protonated state of Hie41 (protonated at N(epsilon)) and Hid41 (protonated at N(delta)), and these findings suggest that Chloroquine may not effectively inhibit the activity of dimeric M(pro)in vivo. Furthermore, three common hot-spot residues of Met165, Hie41, and Gln189 of monomeric M(pro) systems dominated the binding of Ritonavir, Arbidol, and Chloroquine. In dimeric M(pro), Gln189, Met165, and Met49 contributed significantly to binding with Ritonavir, Arbidol, and Saquinavir; therefore, Gln189 and Met165 might serve as the focus in the discovery and development of anti-COVID-19 drugs. In addition, the van der Waals interaction played a significant role in the binding process, and the benzene ring of the drugs showed an apparent inhibitory effect on the normal function of M(pro). The binding cavity had great flexibility to accommodate these different drugs. The results would be notably helpful for enabling a detailed understanding of the binding mechanisms for these important drug-M(pro) interactions and provide valuable guidance for the design of potent inhibitors. Twit Text FOAVip Inhibition mechanism and hot-spot prediction of nine potential drugs for SARS-CoV-2 M(pro) by large-scale molecular dynamic simulations combined with accurate binding free energy calculations ????Nanoscale http://www.kidney.de/pget.php?&tw=1&pmid=33900318 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33900318 #FOAvip English Wikipedia <ref>{{Cite pmid|33900318}}</ref> Inhibition mechanism and hot-spot prediction of nine potential drugs for SARS-CoV-2 M(pro) by large-scale molecular dynamic simulations combined with accurate binding free energy calculations #MMPMID33900318 Luo S; Huang K; Zhao X; Cong Y; Zhang JZH; Duan L Nanoscale 2021[May]; 13 (17): 8313-8332 PMID33900318show ga Coronavirus disease 2019 (COVID-19), which is caused by a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading around the world. However, a universally effective treatment regimen has not been developed to date. The main protease (M(pro)), a key enzyme of SARS-CoV-2, plays a crucial role in the replication and transcription of this virus in cells and has become the ideal target for rational antiviral drug design. In this study, we performed molecular dynamics simulations three times for these complexes of M(pro) (monomeric and dimeric) and nine potential drugs that have a certain effect on the treatment of COVID-19 to explore their binding mechanism. In addition, a total of 12 methods for calculating binding free energy were employed to determine the optimal drug. Ritonavir, Arbidol, and Chloroquine consistently showed an outstanding binding ability to monomeric M(pro) under various methods. Ritonavir, Arbidol, and Saquinavir presented the best performance when binding to a dimer, which was independent of the protonated state of Hie41 (protonated at N(epsilon)) and Hid41 (protonated at N(delta)), and these findings suggest that Chloroquine may not effectively inhibit the activity of dimeric M(pro)in vivo. Furthermore, three common hot-spot residues of Met165, Hie41, and Gln189 of monomeric M(pro) systems dominated the binding of Ritonavir, Arbidol, and Chloroquine. In dimeric M(pro), Gln189, Met165, and Met49 contributed significantly to binding with Ritonavir, Arbidol, and Saquinavir; therefore, Gln189 and Met165 might serve as the focus in the discovery and development of anti-COVID-19 drugs. In addition, the van der Waals interaction played a significant role in the binding process, and the benzene ring of the drugs showed an apparent inhibitory effect on the normal function of M(pro). The binding cavity had great flexibility to accommodate these different drugs. The results would be notably helpful for enabling a detailed understanding of the binding mechanisms for these important drug-M(pro) interactions and provide valuable guidance for the design of potent inhibitors. |*COVID-19[MESH] |*Pharmaceutical Preparations[MESH] |Antiviral Agents/pharmacology[MESH] |Cysteine Endopeptidases/metabolism[MESH] |Humans[MESH] |Molecular Docking Simulation[MESH] |Molecular Dynamics Simulation[MESH] |SARS-CoV-2[MESH]Inhibition mechanism and hot-spot prediction of nine potential drugs f(epmc).pdf DeepDyve Pubget Overpricing