Paper Citing NAMD - Abstract
Jorgensen, Christian; Darre, Leonardo; Vanommeslaeghe, Kenno; Omoto, Kiyoyuki; Pryde, David; Domene, Carmen
In Silico Identification of PAP-1 Binding Sites in the Kv1.2 Potassium Channel
MOLECULAR PHARMACEUTICS, 12:1299-1307, APR 2015
Voltage-gated potassium channels of the Kv1 family play a crucial role in the generation and transmission of electrical signals in excitable cells affecting neuronal and cardiac activities. Small-molecule blockage of these channels has been proposed to occur via a cooperative mechanism involving two main blocking sites: the inner-pore site located below the selectivity filter, and a side-pocket cavity located between the pore and the voltage sensor. Using 0.5 mu s molecular dynamics simulation trajectories complemented by docking calculations, the potential binding sites of the PAP-1 (5-(4-phenoxybutoxy)psoralen) blocker to the crystal structure of Kv1.2 channel have been studied. The presence of both mentioned blocking sites at Kv1.2 is confirmed, adding evidence in favor of a cooperative channel blockage mechanism. These observations provide insight into drug modulation that will guide further developments of Kv inhibitors.
