Compartment-guided assembly of large-scale molecular models with Bentopy

Molecular dynamics simulations of whole cells and organelles aim to transform cell biology by providing a molecular view into the crowded cellular environment. However, constructing suitable starting configurations remains a major bottleneck due to their size and complexity. We present bentopy, a workflow for building cellular-scale models ready for simulation. Bentopy uses a voxel-based spatial representation to efficiently pack molecules into arbitrarily complex compartments. The modular design facilitates the assembly of molecular models containing millions of molecules in minutes on standard workstations. We demonstrate bentopy through three experimentally informed models spanning multiple biological scales. A JCVI-Syn3A whole-cell model combines existing membrane and chromosome structures with diverse cytosolic components. A mitochondrion model integrates cryo-electron tomography maps with spatially resolved proteomics and metabolomics data. An atomistic SARS-CoV-2 virion inside a respiratory aerosol demonstrates bentopy's capability to pack at both atomistic and coarse-grained resolution. Together, these applications establish bentopy as a workflow for constructing simulation-ready models at the cellular scale.