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Title
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Use of restrained molecular dynamics in water to determine three-dimensional protein structure: prediction of the three-dimensional structure of Ecballium elaterium trypsin inhibitor II.
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Authors
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L.Chiche,
C.Gaboriaud,
A.Heitz,
J.P.Mornon,
B.Castro,
P.A.Kollman.
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Ref.
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Proteins, 1989,
6,
405-417.
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PubMed id
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Abstract
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Refinement of distance geometry (DG) structures of EETI-II (Heitz et al.:
Biochemistry 28:2392-2398, 1989), a member of the squash family trypsin
inhibitor, have been carried out by restrained molecular dynamics (RMD) in
water. The resulting models show better side chain apolar/polar surface ratio
and estimated solvation free energy than structures refined "in vacuo." The
consistent lower values of residual NMR constraint violations, apolar/polar
surface ratio, and solvation free energy for one of these refined structures
allowed prediction of the 3D folding and disulfide connectivity of EETI-II.
Except for the few first residues for which no NMR constraints were available,
this computer model fully agreed with X-ray structures of CMTI-I (Bode et al.:
FEBS Lett. 242:285-292, 1989) and EETI-II complexed with trypsin that appeared
after the RMD simulation was completed. Restrained molecular dynamics in water
is thus proved to be highly valuable for refinement of DG structures. Also, the
successful use of apolar/polar surface ratio and of solvation free energy
reinforce the analysis of Novotny et al. (Proteins 4:19-30, 1988) and shows that
these criteria are useful indicators of correct versus misfolded models.
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