A Monte Carlo pharmacophore generation procedure: application to the human PAF receptor.
A novel pharmacophore definition procedure is described, which uses a Monte Carlo method to superimpose molecules. Pharmacophore space is searched by a technique similar to high temperature annealing. Subsequent refinement of candidate pharmacophores by energy minimization produces low-energy conformations that may be involved in receptor binding. The method has been applied to compounds that bind to the human platelet-activating factor (PAF) receptor. Alternative binding site models for the PAF receptor are presented and discussed.
Hodgkin
E E
EE
British Bio-technology Ltd., Oxford, U.K.
Miller
A
A
Whittaker
M
M
D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D066298:In Vitro Techniques; D008956:Models, Chemical; D008958:Models, Molecular; D009010:Monte Carlo Method; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor