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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
Author(s) -
Chiche Laurent,
Gaboriaud Christine,
Heitz Annie,
Mor JeanPaul,
Castro Bertrand,
Kollman Peter A.
Publication year - 1989
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.340060407
Subject(s) - dynamics (music) , trypsin , trypsin inhibitor , biological system , chemistry , biology , biochemistry , physics , acoustics , enzyme
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.