NMR Structure Determination for Larger Proteins Using Backbone-Only Data

See allHide authors and affiliations

Science  04 Feb 2010:
DOI: 10.1126/science.1183649


Conventional protein structure determination from nuclear magnetic resonance data relies heavily on side-chain proton-proton distances. The necessary side-chain resonance assignment, however, is labor-intensive and prone to error. Here, we show that structures can be accurately determined without NMR information on the sidechains for proteins up to 25 kDa by incorporating backbone chemical shifts, residual dipolar couplings, and amide proton distances into the Rosetta protein structure modelling methodology. These data, which are too sparse for conventional methods, serve only to guide conformational search towards the lowest energy conformations in the folding landscape; the details of the computed models are determined by the physical chemistry implicit in the Rosetta all atom energy function. The new method is not hindered by the deuteration required to suppress nuclear relaxation processes for proteins greater than 15 kDa, and should enable routine NMR structure determination for larger proteins.