Protein structure determination by combining sparse NMR data with evolutionary couplings

Yuefeng Tang; Yuanpeng Janet Huang; Thomas A Hopf; Chris Sander; Debora S Marks; Gaetano T Montelione

doi:10.1038/nmeth.3455

Protein structure determination by combining sparse NMR data with evolutionary couplings

Nat Methods. 2015 Aug;12(8):751-4. doi: 10.1038/nmeth.3455. Epub 2015 Jun 29.

Authors

Yuefeng Tang¹, Yuanpeng Janet Huang¹, Thomas A Hopf², Chris Sander³, Debora S Marks⁴, Gaetano T Montelione⁵

Affiliations

¹ 1] Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA. [2] Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
² 1] Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Informatics, Technische Universität München, Garching, Germany.
³ Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
⁴ Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
⁵ 1] Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA. [2] Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA. [3] Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.

Abstract

Accurate determination of protein structure by NMR spectroscopy is challenging for larger proteins, for which experimental data are often incomplete and ambiguous. Evolutionary sequence information together with advances in maximum entropy statistical methods provide a rich complementary source of structural constraints. We have developed a hybrid approach (evolutionary coupling-NMR spectroscopy; EC-NMR) combining sparse NMR data with evolutionary residue-residue couplings and demonstrate accurate structure determination for several proteins 6-41 kDa in size.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Algorithms
Computational Biology / methods*
Crystallography, X-Ray
Evolution, Molecular
Humans
Hydrodynamics
Imaging, Three-Dimensional
Magnetic Resonance Spectroscopy / methods*
Models, Statistical
Molecular Conformation
Protein Conformation
Proteins / chemistry*
Proto-Oncogene Proteins / chemistry
Proto-Oncogene Proteins p21(ras)
ras Proteins / chemistry

Substances

KRAS protein, human
Proteins
Proto-Oncogene Proteins
Proto-Oncogene Proteins p21(ras)
ras Proteins

Associated data

PDB/2N42
PDB/2N44
PDB/2N45
PDB/2N46
PDB/2N47
PDB/2N48
PDB/2N49
PDB/2N4A
PDB/2N4B
PDB/2N4C
PDB/2N4D
PDB/2N4F

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding