Title: CamShift-MD: A novel computational method to determine protein structure using NMR chemical shift

Abstract:
In NMR spectroscopy chemical shifts provide readily measurable and highly sensitive probes of local molecular structure. In structural biology they have thus often been exploited for the validation or refinement of structures of proteins derived from other NMR observables. The determination of three-dimensional protein structures using chemical shifts as the only experimental observable has only recently become possible. The ability to accurately predict chemical shifts is crucial for the performance of these methods. CamShift is a novel predictor that outperforms existing approaches using a computationally efficient equation that is fully differentiable with respect to the positions of the atoms. This equation has successfully been implemented in molecular dynamics code via a pseudo energy function, enabling the direct use of NMR chemical shift measurements in MD simulations for protein structure determination. This approach is particularly suited to perform conformational searches for single structures or ensembles that are difficult or impossible to resolve with current experimental methods, including membrane-bound proteins, folding intermediates, or disease-implicated protein fibrils and aggregates.