Cyclic nucleotide-gated (CNG) channels have a key role in the conversion of sensory information, such as light and scent, into primary electrical signals. CNG channels have, in its N-termini, a transmembrane region which forms the pore of the channel. The C-termini is in the cytoplasmic side and is composed by the called C-linker and the Cyclic Nucleotide Binding Domain (CNBD), both in charge of the gating process after the binding of cyclic nucleotides. In order to understand the gating process, we performed Molecular Dynamic (MD) simulations in presence and absence of cAMP of two structures available in the Protein Data Bank (PDB), which have high sequence homology with CNG channels. In particular, we used one CNBD from M. Loti K+ channels and, from Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) channels, we used a monomer and the complete crystallize structure (C-linker/CNBD tetramer). During 10 ns of free MD we observed small differences between CNBD with and without cAMP. On the other hand, C-linker/CNBD suffers a conformational change upon cAMP binding, which could explain how can be exerted force to the pore region. No large differences were observed between the tetramer with or without ligand. Also, we performed several Steered Molecular Dynamics (SMD) of one monomer alone (both, CNBD and C-linker/CNBD) and when it forms part of the tetramer (C-linker/CNBD). We could follow the different unfolding pathways when cAMP is or is not bounded to the CNBD by using differential contact maps.
