Combined procedure of distance geometry and restrained molecular dynamics techniques for protein structure determination from nuclear magnetic resonance data: Application to the DNA binding domain of lac repressor from Escherichia coli
- 1 January 1988
- journal article
- research article
- Published by Wiley in Proteins-Structure Function and Bioinformatics
- Vol. 3 (4), 209-218
- https://doi.org/10.1002/prot.340030402
Abstract
The technique of two-dimensional nuclear magnetic resonance (2D-NMR) has recently assumed an active role in obtaining information on structures of polypeptides, small proteins, sugars, and DNA fragments in solution. In order to generate spatial structures from the atom-atom distance information obtained by the NMR method, different procedures have been developed. Here we introduce a combined procedure of distance geometry (DG) and molecular dynamics (MD) calculations for generating 3D structures that are consistent with the NMR data set and have reasonable internal energies. We report the application of the combined procedure on the lac repressor DNA binding domain (headpiece) using a set of 169 NOE and 17 “hydrogen bond” distance constraints. Eight of ten structures generated by the distance geometry algorithm were refined within 10 ps MD simulation time to structures with low internal energies that satisfied the distance constraints. Although the combination of DG and MD was designed to combine the good sampling properties of the DG algorithm with an efficient method of lowering the internal energy of the molecule, we found that the MD algorithm contributes significantly to the sampling as well.Keywords
This publication has 22 references indexed in Scilit:
- A comparison of the restrained molecular dynamics and distance geometry methods for determining three‐dimensional structures of proteins on the basis of interproton distancesFEBS Letters, 1987
- 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
- A molecular dynamics study of the C-terminal fragment of the ribosomal proteinJournal of Molecular Biology, 1985
- A protein structure from nuclear magnetic resonance data: lac Repressor headpieceJournal of Molecular Biology, 1985
- Solution conformation of proteinase inhibitor IIA from bull seminal plasma by 1H nuclear magnetic resonance and distance geometryJournal of Molecular Biology, 1985
- Pseudo-structures for the 20 common amino acids for use in studies of protein conformations by measurements of intramolecular proton-proton distance constraints with nuclear magnetic resonanceJournal of Molecular Biology, 1983
- Conformation of glucagon in a lipid-water interphase by 1H nuclear magnetic resonanceJournal of Molecular Biology, 1983
- Sequential resonance assignments as a basis for determination of spatial protein structures by high resolution proton nuclear magnetic resonanceJournal of Molecular Biology, 1982
- A method for constrained energy minimization of macromoleculesJournal of Computational Chemistry, 1980