1gip
From Proteopedia
|
THE NMR STRUCTURE OF DNA DODECAMER DETERMINED IN AQUEOUS DILUTE LIQUID CRYSTALLINE PHASE
Overview
NMR structure determination of nucleic acids presents an intrinsically, difficult problem since the density of short interproton distance contacts, is relatively low and limited to adjacent base pairs. Although residual, dipolar couplings provide orientational information that is clearly, helpful, they do not provide translational information of either a, short-range (with the exception of proton-proton dipolar couplings) or, long-range nature. As a consequence, the description of the nonbonded, contacts has a major impact on the structures of nucleic acids generated, from NMR data. In this paper, we describe the derivation of a potential of, mean force derived from all high-resolution (2 A or better) DNA crystal, structures available in the Nucleic Acid Database (NDB) as of May 2000, that provides a statistical description, in simple geometric terms, of the, relative positions of pairs of neighboring bases (both intra- and, interstrand) in Cartesian space. The purpose of this pseudopotential, which we term a DELPHIC base-base positioning potential, is to bias, sampling during simulated annealing refinement to physically reasonable, regions of conformational space within the range of possibilities that are, consistent with the experimental NMR restraints. We illustrate the, application of the DELPHIC base-base positioning potential to the, structure refinement of a DNA dodecamer, d(CGCGAATTCGCG)(2), for which NOE, and dipolar coupling data have been measured in solution and for which, crystal structures have been determined. We demonstrate by, cross-validation against independent NMR observables (that is, both, residual dipolar couplings and NOE-derived intereproton distance, restraints) that the DELPHIC base-base positioning potential results in a, significant increase in accuracy and obviates artifactual distortions in, the structures arising from the limitations of conventional descriptions, of the nonbonded contacts in terms of either Lennard-Jones van der Waals, and electrostatic potentials or a simple van der Waals repulsion, potential. We also demonstrate, using experimental NMR data for a complex, of the male sex determining factor SRY with a duplex DNA 14mer, which, includes a region of highly unusual and distorted DNA, that the DELPHIC, base-base positioning potential does not in any way hinder unusual, interactions and conformations from being satisfactorily sampled and, reproduced. We expect that the methodology described in this paper for DNA, can be equally applied to RNA, as well as side chain-side chain, interactions in proteins and protein-protein complexes, and side, chain-nucleic acid interactions in protein-nucleic acid complexes., Further, this approach should be useful not only for NMR structure, determination but also for refinement of low-resolution (3-3.5 A) X-ray, data.
About this Structure
1GIP is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Improving the accuracy of NMR structures of DNA by means of a database potential of mean force describing base-base positional interactions., Kuszewski J, Schwieters C, Clore GM, J Am Chem Soc. 2001 May 2;123(17):3903-18. PMID:11457140
Page seeded by OCA on Sun Nov 25 01:23:16 2007
