Φ-value analysis of a linear, sequential reaction mechanism: Theory and application to ion channel gating

Yu Zhou, John E. Pearson, Anthony Auerbach

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

We derive the analytical form of a rate-equilibrium free-energy relationship (with slope Φ) for a bounded, linear chain of coupled reactions having arbitrary connecting rate constants. The results confirm previous simulation studies showing that Φ-values reflect the position of the perturbed reaction within the chain, with reactions occurring earlier in the sequence producing higher Φ-values than those occurring later in the sequence. The derivation includes an expression for the transmission coefficients of the overall reaction based on the rate constants of an arbitrary, discrete, finite Markov chain. The results indicate that experimental Φ-values can be used to calculate the relative heights of the energy barriers between intermediate states of the chain but provide no information about the energies of the wells along the reaction path. Application of the equations to the case of diliganded acetylcholine receptor channel gating suggests that the transition-state ensemble for this reaction is nearly flat. Although this mechanism accounts for many of the basic features of diliganded and unliganded acetylcholine receptor channel gating, the experimental rate-equilibrium free-energy relationships appear to be more linear than those predicted by the theory.

Original languageEnglish
Pages (from-to)3680-3685
Number of pages6
JournalBiophysical Journal
Volume89
Issue number6
DOIs
StatePublished - Dec 2005

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