DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins

Hall-Swan, Sarah; Antunes, Dinler Amaral; Devaurs, Didier; Rigo, Maurício; Kavraki, Lydia E.; Zanatta, Geancarlo

doi:10.1101/2021.01.21.427315

Cited by 2 publications

(3 citation statements)

References 7 publications

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“…Another approach in this regard is DINC−COVID, a user-friendly docking interface developed by Hall-Swan et al published as a preprint in January 2021. 76 This computational tool allows ensemble docking with three SARS-CoV-2 proteins, including the Mpro. Three distinct ensembles for each SARS-CoV-2 protein are available, including data from crystal structures or from MD simulations with different force fields (CHARMM or GROMOS).…”

Section: ■ Introductionmentioning

confidence: 99%

“…Undoubtedly, valuable conclusions would emerge in future papers of these authors with the complete analysis of the data collected. Another approach in this regard is DINC–COVID, a user-friendly docking interface developed by Hall-Swan et al published as a preprint in January 2021 . This computational tool allows ensemble docking with three SARS-CoV-2 proteins, including the Mpro.…”

Section: Introductionmentioning

confidence: 99%

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Strengths and Weaknesses of Docking Simulations in the SARS-CoV-2 Era: the Main Protease (Mpro) Case Study

Llanos

Gantner

Rodríguez

et al. 2021

J. Chem. Inf. Model.

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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.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Strengths and Weaknesses of Docking Simulations in the SARS-CoV-2 Era: the Main Protease (Mpro) Case Study

Llanos

Gantner

Rodríguez

et al. 2021

J. Chem. Inf. Model.

View full text Add to dashboard Cite

show abstract

“…As part of the global response to the COVID-19 pandemic, some existing tools have been adapted, e.g. , ensemble meta-docking for inhibitor identification, , whereas entirely new ones have been introduced, e.g. , a genome browser and a drug-repurposing pipeline …”

Section: Correcting the Coursementioning

confidence: 99%

Reductionism Ad Absurdum: The Misadventures of Structural Biology in the Time of Coronavirus

Svetlov¹,

Artsimovitch

2021

ACS Infect. Dis.

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The tragic consequences of the COVID-19 pandemic have led to admirable responses by the global scientific community, including a profound acceleration in the pace of research and exchange of findings. However, this has had considerable costs of its own, as erroneous conclusions have propagated faster than researchers have been able to detect and correct them. We illustrate the specific misunderstandings that have resulted from reductionist approaches to the study of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which are but one instance of a regrettably growing trend in structural biology. Far from merely being cautionary tales about the conduct of scientific research, these errors have had significant practical impact, by hampering a correct understanding of RdRp structure and mechanism, its inhibition by nucleoside analogues such as remdesivir, and the discovery and characterization of such analogues. After correcting these misunderstandings, we close with several recommendations for a broader correction of the course of scientific research.

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DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins

Cited by 2 publications

References 7 publications

Strengths and Weaknesses of Docking Simulations in the SARS-CoV-2 Era: the Main Protease (Mpro) Case Study

Strengths and Weaknesses of Docking Simulations in the SARS-CoV-2 Era: the Main Protease (Mpro) Case Study

Reductionism Ad Absurdum: The Misadventures of Structural Biology in the Time of Coronavirus

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