Recent Advances in NMR Protein Structure Prediction with ROSETTA

Nuclear magnetic resonance (NMR) spectroscopy is a powerful method for studying the structure and dynamics of proteins in their native state. For high-resolution NMR structure determination, the collection of a rich restraint dataset is necessary. This can be difficult to achieve for proteins with high molecular weight or a complex architecture. Computational modeling techniques can complement sparse NMR datasets (<1 restraint per residue) with additional structural information to elucidate protein structures in these difficult cases. The Rosetta software for protein structure modeling and design is used by structural biologists for structure determination tasks in which limited experimental data is available. This review gives an overview of the computational protocols available in the Rosetta framework for modeling protein structures from NMR data. We explain the computational algorithms used for the integration of different NMR data types in Rosetta. We also highlight new developments, including modeling tools for data from paramagnetic NMR and hydrogen-deuterium exchange, as well as chemical shifts in CS-Rosetta. Furthermore, strategies are discussed to complement and improve structure predictions made by the current state-of-the-art AlphaFold2 program using NMR-guided Rosetta modeling.

Automated summary

Nuclear magnetic resonance (NMR) spectroscopy allows for the study of protein structures and dynamics. Although it can be challenging to collect sufficient NMR data for complex proteins, computational modeling techniques, such as those provided by the Rosetta software, can supplement sparse data and improve structure determination. This review provides an overview of the computational protocols in Rosetta for modeling protein structures from NMR data, including new developments for paramagnetic NMR, hydrogen-deuterium exchange, and chemical shifts.