Development of a conformational search strategy for flexible ligands: a study of the potent mu-selective opioid analgesic fentanyl

An extensive conformational search of the potent opioid analgesic, fentanyl, was performed using the semiempirical quantum mechanical method AM1 and the CHARMm potential energy function. A combination of two procedures was used to search the conformational space for fentanyl, which included nested d...

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Bibliographic Details
Published in:Journal of computer-aided molecular design 1991-08, Vol.5 (4), p.335-356
Main Authors: Cometta-Morini, C, Loew, G H
Format: Article
Language:English
Subjects:
Fentanyl - chemistry
Fentanyl - metabolism
Molecular Conformation
Molecular Structure
Quantum Theory
Receptors, Opioid - metabolism
Receptors, Opioid, mu
Software
Thermodynamics
X-Ray Diffraction
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Summary:An extensive conformational search of the potent opioid analgesic, fentanyl, was performed using the semiempirical quantum mechanical method AM1 and the CHARMm potential energy function. A combination of two procedures was used to search the conformational space for fentanyl, which included nested dihedral scans, geometry optimization and molecular dynamics simulation at different temperatures. In addition, the effect of a continuum solvent environment was taken into account by use of appropriate values for the dielectric constant in the CHARMm computations. The results of the conformational search allowed the determination of the probable conformation of fentanyl in polar and nonpolar solvents and of three candidate conformers for its bioactive form.
ISSN:0920-654X
DOI:10.1007/BF00126667