Abstract

We propose to develop new methods of determining the structural and dynamic implications of nuclear magnetic resonance data on proteins in solution. These methods of analysis will contribute in an essential way to our understanding of protein structure and function, and hence to the solution of many important problems in biology and medicine. The analysis itself consists of three phases: In the first, a large ensemble of protein conformations that are geometrically consistent with the data is computed. In the second, these are refined so that they are also consistent with the established physical and chemical regularities of protein structures. In the third, we attempt to find relative populations and models for the fluctuations in these conformations that enable us to back-calculate the NMR data from the ensemble as a whole.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM038221-07
Application #
3294407
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1990-11-01
Project End
1995-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Najfeld, I; Dayie, K T; Wagner, G et al. (1997) A robust method for estimating cross-relaxation rates from simultaneous fits to build-up and decay curves. J Magn Reson 124:372-82
Yang, J X; Krezel, A; Schmieder, P et al. (1994) An evaluation of least-squares fits to COSY spectra as a means of estimating proton-proton coupling constants. II. Applications to polypeptides. J Biomol NMR 4:827-44
Havel, T F; Najfeld, I; Yang, J X (1994) Matrix decompositions of two-dimensional nuclear magnetic resonance spectra. Proc Natl Acad Sci U S A 91:7962-6
Yee, D P; Chan, H S; Havel, T F et al. (1994) Does compactness induce secondary structure in proteins? A study of poly-alanine chains computed by distance geometry. J Mol Biol 241:557-73
Yang, J X; Havel, T F (1994) An evaluation of least-squares fits to COSY spectra as a means of estimating proton-proton coupling constants. I. Simulated test problems. J Biomol NMR 4:807-26
Yang, J X; Havel, T F (1993) SESAME: a least-squares approach to the evaluation of protein structures computed from NMR data. J Biomol NMR 3:355-60
Hyberts, S G; Goldberg, M S; Havel, T F et al. (1992) The solution structure of eglin c based on measurements of many NOEs and coupling constants and its comparison with X-ray structures. Protein Sci 1:736-51
Wagner, G; Hyberts, S G; Havel, T F (1992) NMR structure determination in solution: a critique and comparison with X-ray crystallography. Annu Rev Biophys Biomol Struct 21:167-98
Havel, T F (1991) An evaluation of computational strategies for use in the determination of protein structure from distance constraints obtained by nuclear magnetic resonance. Prog Biophys Mol Biol 56:43-78
Kochoyan, M; Havel, T F; Nguyen, D T et al. (1991) Alternating zinc fingers in the human male associated protein ZFY: 2D NMR structure of an even finger and implications for ""jumping-linker"" DNA recognition. Biochemistry 30:3371-86

Showing the most recent 10 out of 13 publications