NMR chemical shifts provide important local structural information for proteins. Consistent structure generation from NMR chemical shift data has recently become feasible for proteins with sizes of up to 130 residues, and such structures are of a quality comparable to those obtained with the standard NMR protocol. In collaboration with Dr. David Baker and his group, we have previously developed a chemical-shift-guided approach to successfully and accurately determine structures on the basis of chemical shifts, for systems less than about 130 amino acids. New work focuses on extending this approach to allow incorporation of easily accessible experimental information. By means of an optimized neural network algorithm, SPARTA+, we are able to estimate chemical shifts for proteins of known structure. This in turn provides an important step towards finding fragments in the crystallographic structure database that are compatible in structure with fragments of proteins for which only NMR chemical shift assignments are available. Integration with the previously developed chemical shift Rosetta (CS-Rosetta) program shows significant performance enhancement. Other enhancements in the CS-Rosetta procedure itself make it suitable for determining the structure of homo-oligomeric proteins, as demonstrated for the catalytic core domain of HIV integrase.

Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2011
Total Cost
$399,872
Indirect Cost
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State
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Shen, Yang; Roche, Julien; Grishaev, Alexander et al. (2018) Prediction of nearest neighbor effects on backbone torsion angles and NMR scalar coupling constants in disordered proteins. Protein Sci 27:146-158
Chiliveri, Sai Chaitanya; Louis, John M; Ghirlando, Rodolfo et al. (2018) Tilted, Uninterrupted, Monomeric HIV-1 gp41 Transmembrane Helix from Residual Dipolar Couplings. J Am Chem Soc 140:34-37
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Li, Jingwen; Wang, Yefei; Chen, Jingfei et al. (2016) Observation of ?-Helical Hydrogen-Bond Cooperativity in an Intact Protein. J Am Chem Soc 138:1824-7
Roche, Julien; Ying, Jinfa; Bax, Ad (2016) Accurate measurement of (3)J(HNH?) couplings in small or disordered proteins from WATERGATE-optimized TROSY spectra. J Biomol NMR 64:1-7
Ceccon, Alberto; Tugarinov, Vitali; Bax, Ad et al. (2016) Global Dynamics and Exchange Kinetics of a Protein on the Surface of Nanoparticles Revealed by Relaxation-Based Solution NMR Spectroscopy. J Am Chem Soc 138:5789-92
Shen, Yang; Bax, Ad (2015) Homology modeling of larger proteins guided by chemical shifts. Nat Methods 12:747-50
Mantsyzov, Alexey B; Shen, Yang; Lee, Jung Ho et al. (2015) MERA: a webserver for evaluating backbone torsion angle distributions in dynamic and disordered proteins from NMR data. J Biomol NMR 63:85-95

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