Conformational Analysis of D-tubocurarine: Implications for Minimal Dimensions of Its Binding Site Within Ion Channels

Overview

Journal J Membr Biol

Date 1993 Jul 1

PMID 7692060

Citations 1

Authors

B S Zhorov

N B Brovtsyna

Affiliations

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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.

Citing Articles

Comparison of lowest energy conformations of dimethylcurine and methoxyverapamil: evidence of ternary association of calcium channel, Ca2+, and calcium entry blockers.

Zhorov B J Membr Biol. 1993; 135(2):119-27.

PMID: 8411133 DOI: 10.1007/BF00231437.

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