Generalized open-source workflows for atomistic molecular dynamics simulations of viral helicases

Gigascience. 2024 Jan 2:13:giae026. doi: 10.1093/gigascience/giae026.

Abstract

Viral helicases are promising targets for the development of antiviral therapies. Given their vital function of unwinding double-stranded nucleic acids, inhibiting them blocks the viral replication cycle. Previous studies have elucidated key structural details of these helicases, including the location of substrate binding sites, flexible domains, and the discovery of potential inhibitors. Here we present a series of new Galaxy tools and workflows for performing and analyzing molecular dynamics simulations of viral helicases. We first validate them by demonstrating recapitulation of data from previous simulations of Zika (NS3) and SARS-CoV-2 (NSP13) helicases in apo and complex with inhibitors. We further demonstrate the utility and generalizability of these Galaxy workflows by applying them to new cases, proving their usefulness as a widely accessible method for exploring antiviral activity.

Keywords: Coronavirus; Dengue virus; Galaxy; MERS; NS3; NSP13; RNA virus; SARS-CoV-2; Zika virus; helicase; molecular dynamics simulations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Binding Sites
  • Coronavirus Papain-Like Proteases / chemistry
  • Coronavirus Papain-Like Proteases / metabolism
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism
  • Humans
  • Molecular Dynamics Simulation*
  • RNA Helicases / chemistry
  • RNA Helicases / metabolism
  • SARS-CoV-2* / enzymology
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / metabolism
  • Workflow
  • Zika Virus / enzymology

Substances

  • RNA Helicases
  • DNA Helicases
  • Antiviral Agents
  • papain-like protease, SARS-CoV-2
  • Coronavirus Papain-Like Proteases
  • Viral Nonstructural Proteins