Energetic coupling model for CFTR gating. ATP hydrolysis provides a shortcut from the O1 to O2 state. The C, O1, O2, and O2 ATP states are the same as described in Scheme 2. The O1′ state is added to represent ATP hydrolysis. The C ATP state is added to represent ATP binding before NBD dimerization. The reason for adding the C AD state is described in Discussion.