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 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.
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Srivatsan
S
Raman
Oliver F
OF
Lange
Paolo
P
Rossi
Michael
M
Tyka
Xu
X
Wang
James
J
Aramini
Gaohua
G
Liu
Theresa A
TA
Ramelot
Alexander
A
Eletsky
Thomas
T
Szyperski
Michael A
MA
Kennedy
James
J
Prestegard
Gaetano T
GT
Montelione
David
D
Baker
D003198:Computer Simulation; D008958:Models, Molecular; D009010:Monte Carlo Method; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013816:Thermodynamics
D011506:Proteins