Saturday, February 11, 2012

NMR Structure Determination for Larger Proteins Using Backbone-Only Data

S. Raman, O. F. Lange, P. Rossi, M. Tyka, X. Wang, J. Aramini, G. Liu, T. A. Ramelot, A. Eletsky, T. Szyperski, M. A. Kennedy, J. Prestegard, G. T. Montelioni, D. Baker Science 2010, 327, 1014 (Free access with registration)

Baker and co-wokers present show that inclusion of experimental NMR data for the backbone atoms (chemical shifts, RDC, and HN-HN NOEs) that can be measured relatively easily can help significantly in protein structure determination using ROSETTA.  This CS-RDC-NOE-ROSETTA protocol not only helps guide the conformational search, but also helps alleviate errors in the energy function.

The protocol was tested on 12 protein with up to 266 residues, which is quite large by NMR standards.  For the larger proteins "the computed structures are not completely converged and have large disordered regions.  Furthermore, the method was validated by a blind test on five proteins (with up to 122 residues) in which the CS-RDC-NOE-ROSETTA protocol found satisfactory structures in all cases. 

Another major step forward in protein structure determination from the Baker lab.  I could not find any mentioned of the required CPU time, but it is no doubt substantial.
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