Meso-Soup: A community approach to building a computational description of the biological mesoscale

Physics-based models of biomolecular systems that explicitly represent biomolecular structure and mechanics, such as atomistic molecular dynamics simulations, are well established because experimental data have been available to iteratively improve and validate models. Now, simulations of the biological mesoscale are growing in importance because of the improvements in experimental tools to visualize this regime. This includes techniques such as cryo-electron microscopy and tomography, microscopies that follow individual proteins in their cellular contexts, in situ scattering to follow the dynamic evolution of biomolecular assembly, and omics tools. Together, these approaches, alone and in combination, have revealed the importance of interactomes that bridge multiple scales. Here, we describe the theoretical, computational, and cultural challenges that need to be overcome to gain an understanding of the biological mesoscale and offer potential solutions. This commentary is the result of a joint CECAM/CCPBioSim discussion workshop on how the community should address the challenges of biomolecular simulations at the mesoscale, held in Trento, Italy, in the summer of 2024. The aim is to provide a broad overview of the tools and techniques relevant to the biological mesoscale and to signpost readers to more detailed discussions in the cited literature.