Predicting protein backbone chemical shifts from C? coordinates: extracting high resolution experimental observables from low resolution models.

ABSTRACT: Given the demonstrated utility of coarse-grained modeling and simulations approaches in studying protein structure and dynamics, developing methods that allow experimental observables to be directly recovered from coarse-grained models is of great importance. In this work, we develop one such method that enables protein backbone chemical shifts (1HN, 1H?, 13C?, 13C, 13C?, and 15N) to be predicted from C? coordinates. We show that our C?-based method, LARMORC?, predicts backbone chemical shifts with comparable accuracy to some all-atom approaches. More importantly, we demonstrate that LARMORC? predicted chemical shifts are able to resolve native structure from decoy pools that contain both native and non-native models, and so it is sensitive to protein structure. As an application, we use LARMORC? to characterize the transient state of the fast-folding protein gpW using recently published NMR relaxation dispersion derived backbone chemical shifts. The model we obtain is consistent with the previously proposed model based on independent analysis of the chemical shift dispersion pattern of the transient state. We anticipate that LARMORC? will find utility as a tool that enables important protein conformational substates to be identified by “parsing” trajectories and ensembles generated using coarse-grained modeling and simulations.

SUBMITTER: Frank AT 

PROVIDER: S-EPMC4295808 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature