ISSN:
0020-7608
Schlagwort(e):
Computational Chemistry and Molecular Modeling
;
Atomic, Molecular and Optical Physics
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Chemie und Pharmazie
Notizen:
β-Endorphins are 31 amino acid endogenous opioid peptides with high receptor affinity and antinociceptive activity. Because of their importance as neurohormones and the significant experimental effort that has been made to understand their structure activity profiles, we have begun to develop procedures that could be useful first to identify low-energy conformers of β-endorphins and ultimately their bioactive form. In the initial studies reported here, we have identified plausible initial structures of the full peptide by calculating and comparing the conformational preference of all possible extended tetrapeptide fragments of β-endorphin starting from each of the first 28 residues. Comparisons of fragment energies suggested two types of compact folded β-endorphin conformers were plausible: a helix-turn-helix and an antiparallel β-sheet conformer. These structures, as well as an extended α-helical and β-strand conformer, were assembled and total geometry optimization performed using the empirical-energy-based program AMBER. The results yield an α-helical structure as the lowest energy form consistent with recently reported NMR studies of β-endorphin. The two more compact folded structures obtained, however, are reasonable starting conformations for further planned molecular dynamics simulation studies and could yield competing low-energy structures as candidates for the bioactive form of these peptides.
Zusätzliches Material:
2 Ill.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1002/qua.560340707
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