Solution structures of proteins from NMR data and modeling: alternative folds for neutrophil peptide 5
- 1 November 1989
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 28 (24), 9361-9372
- https://doi.org/10.1021/bi00450a017
Abstract
The structure of neutrophil peptide 5 in solution has recently been reported (Pardi et al., 1988). The structure determination was accomplished by using a distance geometry algorithm and 107 interproton distance constraints obtained from 2D NMR data. In each of the eight independent solutions to the distance geometry equations, the overall fold of the polypeptide backbone was identical and the root mean square (rms) deviation between backbone atoms of the superimposed structures was small (.apprx. 2.4 .ANG.). In this paper we report additional NP-5 structures obtained by using a new structure generation algorithm: a Monte Carlo search in torsion angle space. These structures have a large rms backbone deviation from the distance geometry structures (.apprx. 5.0 .ANG.). The backbone topologies differ in significant respects from the distance geometry structures and from each other. Structures are found that are pseudo mirror images of part or all of the fold corresponding to that first obtained with the distance geometry procedure. For small proteins, the problem of distinguishing the correct structure among pseudo mirror images is likely to be greater than previously recognized. When a set of test distance constraints constructed from a novel Monte Carlo structure is used as input in the distance geometry algorithm, the fold of the resulting structure does not correspond to that of the target. The results also demonstrate that the previously accepted criteria (the magnitude of the rms deviation between multiple solutions of the distance geometry equations) for defining the accuracy and precision of a peptide structure generated from NMR data are inadequate. An energetic analysis of structures corresponding to the different folding topologies has been carried out. The molecular mechanics energies obtained by minimization and molecular dynamics refinement provide sufficient information to eliminate certain alternative structures. On the basis of a careful comparison of the different trial structures with the experimental data, it is concluded that the NP-5 peptide fold which was originally reported is most consistent with the data. An alternative fold corresponding to structures with low energies and small total distance violations is ruled out because for this fold predicted NOEs are not observed experimentally.This publication has 11 references indexed in Scilit:
- Solution structures of the rabbit neutrophil defensin NP-5Journal of Molecular Biology, 1988
- Protein structures in solution by nuclear magnetic resonance and distance geometryJournal of Molecular Biology, 1987
- Three-dimensional structure of proteins determined by molecular dynamics with interproton distance restraints: application to crambin.Proceedings of the National Academy of Sciences, 1986
- Calculation of protein conformations by proton-proton distance constraintsJournal of Molecular Biology, 1985
- Solution conformation of a heptadecapeptide comprising the DNA binding helix F of the cyclic AMP receptor protein of Escherichia coliJournal of Molecular Biology, 1985
- Primary structures of six antimicrobial peptides of rabbit peritoneal neutrophils.Journal of Biological Chemistry, 1985
- Solution conformation of proteinase inhibitor IIA from bull seminal plasma by 1H nuclear magnetic resonance and distance geometryJournal of Molecular Biology, 1985
- An evaluation of the combined use of nuclear magnetic resonance and distance geometry for the determination of protein conformations in solutionJournal of Molecular Biology, 1985
- Motional averaging of proton nuclear Overhauser effects in proteins. Predictions from a molecular dynamics simulation of lysozymeJournal of the American Chemical Society, 1984
- Conformation of amino acid side-chains in proteinsJournal of Molecular Biology, 1978