title: Refinement of the thrombin-bound structure of a hirudin peptide by a restrained electrostatically driven Monte Carlo method.
abstract: 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.
authors.affiliation: Biotechnology Research Institute, National Research Council of Canada, Montreal, Québec.
authors.forename: D R
authors.initials: DR
authors.lastname: Ripoll
authors.forename: F
authors.initials: F
authors.lastname: Ni
mesh_terms: D004563:Electrochemistry; D006629:Hirudins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009010:Monte Carlo Method; D011487:Protein Conformation; D013816:Thermodynamics; D013917:Thrombin / Q000378:metabolism*
chemical_list: D006629:Hirudins; D013917:Thrombin