title: Conformational analysis of d-tubocurarine: implications for minimal dimensions of its binding site within ion channels.
abstract: All the minimum-energy conformations of d-tubocurarine were calculated by the method of molecular mechanics. The energy was minimized from 413 closed forms of the 18-member ring. The set of minimum-energy conformations includes 10 forms with energies less than 6 kcal/mol from the most stable one. Among the four lowest minimum-energy conformations, two forms correspond to those known from X-ray studies, whereas two conformations were not detected experimentally earlier. The flexibility of d-tubocurarine was estimated by calculating six paths of interconversion between the four lowest minimum-energy conformations. Using a molecular graphics technique, it was found that the most extended minimum-energy conformation of d-tubocurarine may fit in an ion channel of a rectangular profile of 8.7 x 11.2 A, while one tetrahydroisoquinoline head may fit a profile as small as 6.9 x 11.0 A. A possible model of d-tubocurarine location within the ion channel of the neuronal nicotinic acetylcholine receptor is suggested.
authors.affiliation: Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg.
authors.forename: B S
authors.initials: BS
authors.lastname: Zhorov
authors.forename: N B
authors.initials: NB
authors.lastname: Brovtsyna
mesh_terms: D001665:Binding Sites; D007473:Ion Channels / Q000378:metabolism*; D008956:Models, Chemical; D009474:Neurons / Q000648:ultrastructure; D011487:Protein Conformation; D011950:Receptors, Cholinergic / Q000032:analysis / Q000378:metabolism; D014403:Tubocurarine / Q000737:chemistry* / Q000378:metabolism
chemical_list: D007473:Ion Channels; D011950:Receptors, Cholinergic; D014403:Tubocurarine