Molecular dynamics simulations of scorpion toxin recognition by the Ca(2+)-activated potassium channel KCa3.1.

ABSTRACT: The Ca(2+)-activated channel of intermediate-conductance (KCa3.1) is a target for antisickling and immunosuppressant agents. Many small peptides isolated from animal venoms inhibit KCa3.1 with nanomolar affinities and are promising drug scaffolds. Although the inhibitory effect of peptide toxins on KCa3.1 has been examined extensively, the structural basis of toxin-channel recognition has not been understood in detail. Here, the binding modes of two selected scorpion toxins, charybdotoxin (ChTx) and OSK1, to human KCa3.1 are examined in atomic detail using molecular dynamics (MD) simulations. Employing a homology model of KCa3.1, we first determine conduction properties of the channel using Brownian dynamics and ascertain that the simulated results are in accord with experiment. The model

SUBMITTER: Chen R 

PROVIDER: S-EPMC3797572 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature