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10.1021/acs.jcim.1c00404 http://scihub22266oqcxt.onion/10.1021/acs.jcim.1c00404 34313128!ä!34313128 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Chem+Inf+Model 2021 ; 61 (8): 3758-3770 Nephropedia Template TP {{tp|p=34313128|t=2021. Strengths and Weaknesses of Docking Simulations in the SARS-CoV-2 Era: the Main Protease (Mpro) Case Study |pdf=|usr=}}{{34313128}} gab.com Text Strengths and Weaknesses of Docking Simulations in the SARS-CoV-2 Era: the Main Protease (Mpro) Case Study JO: J Chem Inf Model http://www.kidney.de/pget.php?&tw=1&pmid=34313128 #FOAvip The scientific community is working against the clock to arrive at therapeutic interventions to treat patients with COVID-19. Among the strategies for drug discovery, virtual screening approaches have the capacity to search potential hits within millions of chemical structures in days, with the appropriate computing infrastructure. In this article, we first analyzed the published research targeting the inhibition of the main protease (Mpro), one of the most studied targets of SARS-CoV-2, by docking-based methods. An alarming finding was the lack of an adequate validation of the docking protocols (i.e., pose prediction and virtual screening accuracy) before applying them in virtual screening campaigns. The performance of the docking protocols was tested at some level in 57.7% of the 168 investigations analyzed. However, we found only three examples of a complete retrospective analysis of the scoring functions to quantify the virtual screening accuracy of the methods. Moreover, only two publications reported some experimental evaluation of the proposed hits until preparing this manuscript. All of these findings led us to carry out a retrospective performance validation of three different docking protocols, through the analysis of their pose prediction and screening accuracy. Surprisingly, we found that even though all tested docking protocols have a good pose prediction, their screening accuracy is quite limited as they fail to correctly rank a test set of compounds. These results highlight the importance of conducting an adequate validation of the docking protocols before carrying out virtual screening campaigns, and to experimentally confirm the predictions made by the models before drawing bold conclusions. Finally, successful structure-based drug discovery investigations published during the redaction of this manuscript allow us to propose the inclusion of target flexibility and consensus scoring as alternatives to improve the accuracy of the methods. Twit Text FOAVip Strengths and Weaknesses of Docking Simulations in the SARS-CoV-2 Era: the Main Protease (Mpro) Case Study ????J Chem Inf Model http://www.kidney.de/pget.php?&tw=1&pmid=34313128 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34313128 #FOAvip English Wikipedia <ref>{{Cite pmid|34313128}}</ref> Strengths and Weaknesses of Docking Simulations in the SARS-CoV-2 Era: the Main Protease (Mpro) Case Study #MMPMID34313128 Llanos MA; Gantner ME; Rodriguez S; Alberca LN; Bellera CL; Talevi A; Gavernet L J Chem Inf Model 2021[Aug]; 61 (8): 3758-3770 PMID34313128show ga The scientific community is working against the clock to arrive at therapeutic interventions to treat patients with COVID-19. Among the strategies for drug discovery, virtual screening approaches have the capacity to search potential hits within millions of chemical structures in days, with the appropriate computing infrastructure. In this article, we first analyzed the published research targeting the inhibition of the main protease (Mpro), one of the most studied targets of SARS-CoV-2, by docking-based methods. An alarming finding was the lack of an adequate validation of the docking protocols (i.e., pose prediction and virtual screening accuracy) before applying them in virtual screening campaigns. The performance of the docking protocols was tested at some level in 57.7% of the 168 investigations analyzed. However, we found only three examples of a complete retrospective analysis of the scoring functions to quantify the virtual screening accuracy of the methods. Moreover, only two publications reported some experimental evaluation of the proposed hits until preparing this manuscript. All of these findings led us to carry out a retrospective performance validation of three different docking protocols, through the analysis of their pose prediction and screening accuracy. Surprisingly, we found that even though all tested docking protocols have a good pose prediction, their screening accuracy is quite limited as they fail to correctly rank a test set of compounds. These results highlight the importance of conducting an adequate validation of the docking protocols before carrying out virtual screening campaigns, and to experimentally confirm the predictions made by the models before drawing bold conclusions. Finally, successful structure-based drug discovery investigations published during the redaction of this manuscript allow us to propose the inclusion of target flexibility and consensus scoring as alternatives to improve the accuracy of the methods. |*COVID-19[MESH] |*SARS-CoV-2[MESH] |Humans[MESH] |Molecular Docking Simulation[MESH] |Peptide Hydrolases[MESH]Strengths and Weaknesses of Docking Simulations in the SARS-CoV-2 Era:(epmc).pdf DeepDyve Pubget Overpricing