A method for determining overall protein fold from NMR distance restraints

SummaryWe describe a simple method for determining the overall fold of a polypeptide chain from NOE-derived distance restraints. The method uses a reduced representation consisting of two particles per residue, and a force field containing pseudo-bond and pseudo-angle terms, an ‘electrostatic’ term, but no van der Waals or hard shell repulsive terms. The method is fast and robust, requiring relatively few distance restraints to approximate the correct fold, and the correct mirror image is readily determined. The method is easily implemented using commercially available molecular modeling software.

[1]  Timothy F. Havel,et al.  The sampling properties of some distance geometry algorithms applied to unconstrained polypeptide chains: A study of 1830 independently computed conformations , 1990, Biopolymers.

[2]  A. Gronenborn,et al.  Determination of three‐dimensional structures of proteins from interproton distance data by hybrid distance geometry‐dynamical simulated annealing calculations , 1988, FEBS letters.

[3]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1977, Journal of molecular biology.

[4]  A. Gronenborn,et al.  Solution structure of recombinant hirudin and the Lys-47----Glu mutant: a nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study. , 1990, Biochemistry.

[5]  Gordon M. Crippen,et al.  Distance Geometry and Molecular Conformation , 1988 .

[6]  T. James,et al.  Generation of high-resolution protein structures in solution from multidimensional NMR. , 1991, Annual review of physical chemistry (Print).

[7]  Jeffrey C. Hoch,et al.  An Amateur Looks at Error Analysis in the Determination of Protein Structure by NMR , 1991 .

[8]  C. Beddell,et al.  An x-ray study of the structure and binding properties of iodine-inactivated lysozyme. , 1975, Journal of molecular biology.

[9]  M. Nilges,et al.  Three-dimensional structure of phoratoxin in solution: combined use of nuclear magnetic resonance, distance geometry, and restrained molecular dynamics , 1987 .

[10]  Jeffrey C. Hoch,et al.  Computational Aspects of the Study of Biological Macromolecules by Nuclear Magnetic Resonance Spectroscopy , 1991, NATO ASI Series.

[11]  A M Gronenborn,et al.  Determination of the three-dimensional solution structure of the antihypertensive and antiviral protein BDS-I from the sea anemone Anemonia sulcata: a study using nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing. , 1989, Biochemistry.

[12]  M. Teeter,et al.  Water structure of a hydrophobic protein at atomic resolution: Pentagon rings of water molecules in crystals of crambin. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Timothy F. Havel,et al.  A distance geometry program for determining the structures of small proteins and other macromolecules from nuclear magnetic resonance measurements of intramolecular1H−1H proximities in solution , 1984 .

[14]  M. Levitt,et al.  Computer simulation of protein folding , 1975, Nature.