On the basis of an elaborate conformational analysis of m1- and m2-selective antagonists a respective pharmacophore was deduced. This then was introduced into models of the two muscarinic receptor subtypes. These models were constructued starting from bacteriorhodopsin as a template in accordance with alignment data and mutation experiments. The validity of the interaction geometries between ligands and receptor subtypes is supported by a significant correlation between calculated interaction energies and experimentally determined affinity data.
机构:
King Saud Univ, Coll Sci, Dept Stat & Operat Res, Riyadh 11451, Saudi ArabiaKing Saud Univ, Coll Sci, Dept Stat & Operat Res, Riyadh 11451, Saudi Arabia
机构:
Harvard Med Sch, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA USA
West Virginia Univ, Sch Med, 1 Med Ctr Dr, Morgantown, WV USAHarvard Med Sch, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA USA
Joseph, Lauren
Thomsen, Morgane
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机构:
Harvard Med Sch, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA USA
Psychiat Ctr Copenhagen, Lab Neuropsychiat, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark
Univ Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, DenmarkHarvard Med Sch, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA USA