In response to the COVID-19 disease, BioExcel launched a series of actions to support research on SARS-CoV-2 already in March 2020, and our experts are supporting research through a variety of data sharing initiatives and a dedicated molecular dynamics repository.
In the coming months, we will highlight different aspects of these actions that are relevant to the industry community, and encourage you to reach out to us via industry@bioexcel.eu if you would like to use BioExcel tools and workflows in your own research.
BioExcel’s work on targeting the RNA-dependent RNA polymerase (RdRp; Figure 1) involves teams of the Max Planck Gesellschaft, the Utrecht University, the University of Jyväskylä and The Royal Institute of Technology in Stockholm KTH.
Model of the RNA-dependent RNA polymerase (RdRp).
Some of the main steps carried out so far involved the BioExcel software HADDOCK, CP2K, GROMACS, and pmx:
- Modelling of the RdRp complex (Figure 1) with a state-of-the-art molecular modelling suite
- Target-based screening against approved drugs using HADDOCK yielded Remdesivir, Favipiravir, and Sofosbuvir as top 3 hits
- Calculating partial charges for triphosphate nucleotide inhibitors with CP2K
- Classical molecular dynamics with GROMACS to sample the interactions between each inhibitor and the RdRp-RNA-NTP binding pocket (trajectories accessible via the BioExcel and MOLSSI COVID-19 repositories)
- Free energy calculations with pmx to study the effect of inserting inhibitors at different positions in the RNA primer strand
- QM/MM umbrella sampling calculations to model the reaction pathway for Remdesivir triphosphate hydrolysis with the GMX-CP2K interface
The results will be published soon, so stay tuned for more news.
