The Role of Proton Transport in Gating Current in a Voltage Gated Ion Channel, as Shown by Quantum Calculations

Alisher M Kariev; Michael E Green

THERMODYNAMICS OF AMINO ACID INTERACTIONS: it should be possible to find whether two residues interact by looking at the change in open probability (P o ), and gating current and charge, with mutations of the residues, through mutant cycle analysis. One can also determine the free energy changes associated with the mutations. In this method one performs two single mutations, and then the double mutation. If the double mutation ΔG is not equal to the sum of the two single mutation ΔG values, one concludes that the two residues must interact. Here, the cycle would include states as shown by Fig. 4 (except for notation, this is essentially the same diagram as is given in many papers on mutant cycle analysis). A brief summary of this type of analysis, under the name "linkage analysis", by Shem-Ad and Yifrach, provides a useful discussion of the method (103); these authors trace its conceptual history back to Wyman (104) , in 1964.