Progressive Backmapping of Highly Coarse-Grained Protein Models.

Reconstructing all-atom (AA) structures from highly coarse-grained (HCG) models remains a significant challenge in multiscale molecular dynamics (MD) simulations, particularly for mesoscale biomolecular assemblies that are beyond the reach of conventional MD methods. Building upon ProNet Backmapping, a neural-network-based thermodynamically consistent approach, we introduce a progressive backmapping framework that reconstructs AA models in a stepwise manner across neighboring resolutions, for example, from a 3-residue-per-site HCG model to a 1-residue-per-site model, then to an AA model. This progressive backmapping method achieves high accuracy across a wide range of proteins and effectively reconstructs flexible linkers in multidomain architectures. Moreover, it supports hierarchical reconstruction of complex protein assemblies, including multiple virus-like particles spanning tens of nanometers and containing hundreds of subunits. Using this framework, we demonstrate-for the first time-the ability to hierarchically backmap entire viral assemblies from HCG to full AA resolution, covering at least three different resolutions. Overall, our method provides a scalable framework for incorporating atomistic detail into mesoscale simulations of complex systems across many applications in chemistry and biology.