De novo structure generation using chemical shifts for proteins with high-sequence identity but different folds.
Proteins with high-sequence identity but very different folds present a special challenge to sequence-based protein structure prediction methods. In particular, a 56-residue three-helical bundle protein (GA(95)) and an alpha/beta-fold protein (GB(95)), which share 95% sequence identity, were targets in the CASP-8 structure prediction contest. With only 12 out of 300 submitted server-CASP8 models for GA(95) exhibiting the correct fold, this protein proved particularly challenging despite its small size. Here, we demonstrate that the information contained in NMR chemical shifts can readily be exploited by the CS-Rosetta structure prediction program and yields adequate convergence, even when input chemical shifts are limited to just amide (1)H(N) and (15)N or (1)H(N) and (1)H(alpha) values.
Shen
Yang
Y
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
Bryan
Philip N
PN
He
Yanan
Y
Orban
John
J
Baker
David
D
Bax
Ad
A
D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D011506:Proteins