Docking and MD simulations of the interaction of the tarantula peptide psalmotoxin-1 with ASIC1a channels using a homology model.

The interaction of the tarantula toxin PcTx1 with the hASIC1a ion channel is investigated here along homology modeling (using the crystal structure of the cASIC1 channel as a template and the known sequence of hASIC1a), automated docking (using the NMR solution structure of PcTx1), and molecular dynamics simulations (taking into account proton-binding sites), in what represents the first modeling and computational chemistry in the whole family of ASIC/DEG/ENaCs/FaNaCh channels. The results agree with binding and electrophysiological data for the interaction of mutant (125)I-PcTx1Y(N) with rASIC1a chimeras and PcTx1 itself with hASIC1a chimeras. They go even farther by revealing that only two hASIC1a subunits can be directly involved in the binding, to which four domains - instead of the only two identified by the experiments - participate. Mapping the closest lying amino acids of the homology model and PcTx1 can have heuristic value in stimulating ideas, software, and experimentation.