ISSN:
0887-3585
Keywords:
protein tertiary structure
;
incorrect and correct folding
;
molecular surfaces
;
solvation free energy
;
solution and crystal structure
;
disulfide connectivity determination
;
squash inhibitor family
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Medicine
Notes:
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 cacuo.” The consistent lower values of residual NMR constraint violations, apolar/polar surface ration and solvation free energy of 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 agree with X-ray structures of CMTI-I (Boe 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 n water is thus proved to highly valuable for refinement of DG structures Also, the successful use of apolar/polar surface ratio and 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.
Additional Material:
8 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/prot.340060407
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