New methods of structure refinement for macromolecular structure determination by NMR

New methods of structure refinement for macromolecular structure determination by NMR

Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520

Abstract

Recent advances in multidimensional NMR methodology have permitted solution structures of proteins in excess of 250 residues to be solved. In this paper, we discuss several methods of structure refinement that promise to increase the accuracy of macromolecular structures determined by NMR. These methods include the use of a conformational database potential and direct refinement against three-bond coupling constants, secondary ¹³C shifts, ¹H shifts, T₁/T₂ ratios, and residual dipolar couplings. The latter two measurements provide long range restraints that are not accessible by other solution NMR parameters.

Footnotes

↵ * To whom reprint requests should be addressed. e-mail: clore{at}vger.niddk.nih.gov and gronenborn{at}vger.niddk.nih.gov.
This paper was presented at the colloquium “Computational Biomolecular Science,” organized by Russell Doolittle, J. Andrew McCammon, and Peter G. Wolynes, held September 11–13, 1997, sponsored by the National Academy of Sciences at the Arnold and Mabel Beckman Center in Irvine, CA.
ABBREVIATIONS:

2D,

two-dimensional;

NOE,

nuclear Overhauser effect