Article

NMR Structure Determination for Larger Proteins Using Backbone-Only Data

Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Science (Impact Factor: 33.61). 02/2010; 327(5968):1014-8. DOI: 10.1126/science.1183649
Source: PubMed

ABSTRACT

Conventional protein structure determination from nuclear magnetic resonance data relies heavily on side-chain proton-to-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 nuclear magnetic resonance (NMR) information on the side chains for proteins
up to 25 kilodaltons by incorporating backbone chemical shifts, residual dipolar couplings, and amide proton distances into
the Rosetta protein structure modeling methodology. These data, which are too sparse for conventional methods, serve only
to guide conformational search toward 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 kilodaltons and should enable
routine NMR structure determination for larger proteins.

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Available from: James M Aramini, Mar 10, 2015
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