Tryptophan-47 rotational isomerization in variant-3 scorpion neurotoxin. A combination thermodynamic perturbation and umbrella sampling study

C. Haydock, J. C. Sharp, F. G. Prendergast

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31 Scopus citations

Abstract

A combination thermodynamic perturbation and umbrella sampling study predicts two free energy wells for the rotational isomerization of the variant-3 scorpion neurotoxin tryptophan-47 indole side chain. One well has the indole side chain in the crystallographic orientation; the other has the indole rotated approximately 220 degrees to form a new conformation with a relative free energy of 3 +/- 2 kcal/mol. The activation barrier is 8.5 kcal/mol from the crystallographic well, from which transition state theory predicts a rate of escape of 2 x 10(5) s-1. Correlations in the displacements of side chains neighboring tryptophan-47 and the isomerization reaction coordinate last up to 20 ps. Favorable conditions of experimental verification are discussed.

Original languageEnglish (US)
Pages (from-to)1269-1279
Number of pages11
JournalBiophysical Journal
Volume57
Issue number6
DOIs
StatePublished - 1990

ASJC Scopus subject areas

  • Biophysics

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