NMR Structure Determination for Larger Proteins Using Backbone-Only Data

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2010-02, Vol.327 (5968), p.1014-1018
Main Authors: Raman, Srivatsan, Lange, Oliver F, Rossi, Paolo, Tyka, Michael, Wang, Xu, Aramini, James, Liu, Gaohua, Ramelot, Theresa A, Eletsky, Alexander, Szyperski, Thomas, Kennedy, Michael A, Prestegard, James, Montelione, Gaetano T, Baker, David
Format: Article
Language:English
Subjects:
Biochemistry
Biological and medical sciences
Computer Simulation
Data lines
Energy
Experimental data
Fundamental and applied biological sciences. Psychology
Mathematical minima
Models, Molecular
Molecular biology
Molecular biophysics
Molecular structure
Monte Carlo Method
NMR
Nuclear magnetic resonance
Nuclear Magnetic Resonance, Biomolecular - methods
Nuclear structure
Protein Conformation
Protein Folding
Proteins
Proteins - chemistry
Research design
Software
Statistical median
Structure in molecular biology
Thermodynamics
Trajectories
Tridimensional structure
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1183649