Key result
F103A mutation prevents KcsA inactivation by removing unfavorable steric interactions with the Ile100 side chain.
Why the study?
The thermodynamic basis for the coupling between activation and inactivation gating in potassium channels was not quantitatively elucidated.
Population
KcsA potassium channels including F103A and I100A mutants
Comparison
F103A and I100A mutations vs wild-type KcsA channels
Design
Free energy perturbation molecular dynamics simulations with experimental validation
Authors
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Mechanistic insight into KcsA gating is hypothesis-generating; leaves open relevance to human cardiac potassium channels.
Molecular dynamics simulations reveal that steric interactions between specific residues (Phe103 and Ile100) couple activation and inactivation gating in KcsA potassium channels.
Pan et al. (2011) studied this question. F103A and I100A mutations in KcsA channels vs. Wild-type KcsA was evaluated on Thermodynamic basis for coupling between intracellular gate and selectivity filter. Free energy molecular dynamics simulations revealed that the absence of inactivation in the F103A mutation in KcsA is due to the absence of unfavorable steric interaction with the Ile100 side chain.
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