To date, interpretation of isotropic chemical shifts in structural terms is largely based on empirical correlations gained from the mining of protein chemical shifts deposited in the BMRB, in conjunction with the known corresponding 3D structures. Chemical-Shift-ROSETTA (CS-ROSETTA) is a robust protocol to exploit this relation for de novo protein structure generation, using as input parameters the 13Ca, 13Cb, 13C', 15N, 1H and 1HN NMR chemical shifts. These shifts are generally available at the early stage of the traditional NMR structure determination procedure, prior to the collection and analysis of structural restraints. CS-ROSETTA approach, as shown below, utilizes SPARTA-based selection of protein fragments from the PDB, in conjunction with a regular ROSETTA Monte Carlo assembly and relaxation method. Evaluation of 16 proteins, varying in size from 56 to 129 residues yielded full atom models that have 0.7-1.8 angstrom root-mean-square deviations for the backbone atoms relative to the experimentally determined X-ray or NMR structures. The strategy also has been successfully applied in a blind manner to eight structural genomics targets with molecular weights up to 16 kDa, whose conventional NMR structure determination was conducted in parallel. This protocol potentially provides a new direction for high-throughput NMR structure determination, in particular in structural genomics.

Author: Yang Shen

Version: n/a

Reference: Proc Natl Acad Sci USA, (2008) early edition

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