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Title
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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.
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Authors
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J.de Vlieg,
R.M.Scheek,
W.F.van Gunsteren,
H.J.Berendsen,
R.Kaptein,
J.Thomason.
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Ref.
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Proteins, 1988,
3,
209-218.
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PubMed id
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Abstract
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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.
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