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. 2021 Jul 15;81(14):2929–2943.e6. doi: 10.1016/j.molcel.2021.05.033

Figure 5.

Figure 5

Pore hydration and ivabradine docking in HCN4 structures

(A and B) Representative snapshot from unrestrained MD simulation of PD of HCN4 structure with narrow cytosolic entrance (blue, holo) (A) and with wider cytosolic entrance (B) (green, apo/AM; identical results were obtained with apo/LC). Two subunits of tetramer are shown for clarity. In (A), Y507, I511, T515, and Q519 side chains occupy cavity and do not allow passage of water molecules (red and white sticks and balls) and K+ ions (blue spheres) through bundle crossing. In (B), a different conformation of S6 allows water and K+ ions to pass through bundle crossing and enter inner pore cavity.

(C and D) Docking of ivabradine in two PDs (colored as above, with orange mesh representing ivabradine density). In (C), the narrow constriction created by Q519 prevents ivabradine entry into cavity. In (D), ivabradine enters in cavity and explores several positions, including one (ivabradine shown in orange sticks) in close proximity with Y507 and I511 (highlighted in red).