Machine Learning augmented docking studies of aminothioureas at the SARS-CoV-2-ACE2 interface

PLoS One. 2021 Sep 9;16(9):e0256834. doi: 10.1371/journal.pone.0256834. eCollection 2021.

Abstract

The current pandemic outbreak clearly indicated the urgent need for tools allowing fast predictions of bioactivity of a large number of compounds, either available or at least synthesizable. In the computational chemistry toolbox, several such tools are available, with the main ones being docking and structure-activity relationship modeling either by classical linear QSAR or Machine Learning techniques. In this contribution, we focus on the comparison of the results obtained using different docking protocols on the example of the search for bioactivity of compounds containing N-N-C(S)-N scaffold at the S-protein of SARS-CoV-2 virus with ACE2 human receptor interface. Based on over 1800 structures in the training set we have predicted binding properties of the complete set of nearly 600000 structures from the same class using the Machine Learning Random Forest Regressor approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antiviral Agents / pharmacology*
  • Humans
  • Machine Learning*
  • Molecular Dynamics Simulation*
  • Protein Binding
  • SARS-CoV-2 / chemistry*
  • Thiourea / chemistry
  • Thiourea / pharmacology*

Substances

  • Antiviral Agents
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Thiourea

Grants and funding

This research was partly supported by the Foundation for Polish Science via the grant MAB PLUS/2019/11 The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. FQS Poland provided support in the form of salaries for one of the authors [W.P.], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the ‘author contributions’ section.