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

Area of Science:

• Biochemistry
• Virology
• Computational Biology

Background:

• Viral helicases are essential for viral replication and represent promising antiviral drug targets.
• Understanding viral helicase structure and function is key to developing effective antiviral therapies.
• Previous research has identified key structural features and potential inhibitors of viral helicases.

Purpose of the Study:

• To introduce new Galaxy tools and workflows for molecular dynamics (MD) simulations of viral helicases.
• To validate these tools by reproducing existing simulation data for Zika and SARS-CoV-2 helicases.
• To demonstrate the broad applicability of these workflows for investigating antiviral activity.

Main Methods:

• Development and implementation of novel Galaxy tools for MD simulations.
• Performing simulations of viral helicases (Zika NS3, SARS-CoV-2 NSP13) in apo and inhibitor-bound states.
• Analysis of simulation data to assess viral helicase behavior and inhibitor interactions.

Main Results:

• Successful validation of Galaxy workflows by recapitulating previously published simulation data.
• Demonstration of the tools' utility and generalizability across different viral helicase systems.
• Confirmation of the workflows' effectiveness in exploring antiviral potential.

Conclusions:

• The presented Galaxy tools and workflows provide a widely accessible platform for MD simulations of viral helicases.
• These computational resources can significantly aid in the discovery and development of novel antiviral agents.
• This approach facilitates the exploration of structure-activity relationships for viral helicase inhibitors.