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Refinement of the thrombin‐bound structure of a hirudin peptide by a restrained electrostatically driven Monte Carlo method
Author(s) -
Ripoll Daniel R.,
Ni Feng
Publication year - 1992
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360320411
Subject(s) - chemistry , energy minimization , folding (dsp implementation) , nuclear overhauser effect , monte carlo method , helix (gastropod) , crystallography , peptide , stereochemistry , nuclear magnetic resonance spectroscopy , computational chemistry , ecology , biochemistry , statistics , mathematics , snail , electrical engineering , biology , engineering
Energy refinement of the structure of a linear peptide, hirudin56–65, bound to thrombin was carried out using a conformational search method in combination with restrained minimization. Five conformations originated from nmr data and distance geometry calculations having a similar global folding pattern but quite different backbone conformations were used as the starting structures. As a result of this approach, a series of low‐energy conformations compatible with a set of upper and lower bounds of interproton distances determined from transferred nuclear Overhauser effects were found. A comparison among the lowest energy conformations of each run showed that the combination of energy refinement plus distance constraints led to a very well‐defined structure for both the backbone and the side chains of the last 7 residues of the polypeptide. Furthermore, the low‐energy conformations generated with this technique contain a segment of 3 10 ‐helix involving the last 5 residues at the COOH terminal end.