Layne Frechette - Computational modeling of virus assembly in biomolecular condensates

Abstract: Biomolecular condensates have recently emerged as a powerful means to compartmentalize and regulate cellular processes. Many viruses create condensates within their host cells, potentially enabling regulation of viral replication and assembly in space and time. Such regulation could, for example, assist viruses in selectively packaging their genomes amidst a vast excess of host cellular RNAs. Yet, the mechanisms by which condensates facilitate assembly are not well understood. Here, I will discuss computational modelling to investigate how selective partitioning of viral components into condensates affects assembly and genome packaging. I will first describe coarse-grained molecular dynamics simulations of empty capsid assembly. The simulations show that condensates can enhance the rate and yield of capsid assembly by orders of magnitude. Additionally, condensates can create classes of assembly pathways that are unseen in bulk assembly. Next, I will describe a rate equation model for condensate-mediated genome packaging. We find that condensates enable extremely selective packaging of viral genomes. Moreover, recent work has shown that some viral condensates recruit ribosomes, and we show that the resulting localized production of capsid subunits can further enhance packaging selectivity. Our work suggests that condensates can be a powerful means to facilitate capsid assembly and genome packaging and thus are potential antiviral drug targets. More broadly, the mechanisms that we have identified could facilitate rapid and selective cargo encapsulation in diverse biological or human-engineered systems.

Biosketch - Dr. Frechette is a postdoctoral fellow at Brandeis University. Here is his Google Scholar link. He earned his PhD in Physical Chemistry from UC Berkeley in 2020 with a thesis entitled "“Chemical Transformations of Nanocrystals: Theory and Molecular Simulation,” with Phillip Geissler. He then had a 2-year postdoc at NIH (NIDDK) working with Robert Best. In 2022, he moved to Brandeis, where he works with Michael Hagan and Aparna Baskaran.