Paper Citing NAMD - Abstract
Chen, Rong; Chung, Shin-Ho
Conserved Functional Surface of Antimammalian Scorpion beta-Toxins
JOURNAL OF PHYSICAL CHEMISTRY B, 116:4796-4800, APR 26 2012
Scorpion beta-toxins bind to the voltage-sensing domain of voltage-gated sodium (Na-v) channels and trap the voltage-sensing domain in the activated state. Two structurally similar beta-toxins from scorpions, Css4 and Cn2, selectively target different subtypes of mammalian Na-v channels. While the receptor site on the channels is known, the functional surface of the toxins remains to be understood. Here, we predict the binding modes of Css4 and Cn2 to the voltage-sensing domains of Na(v)1.2 and Na(v)1.6, respectively, with a molecular docking method and molecular dynamics simulations. The dissociation constants for the predicted toxin-channel complexes derived with umbrella sampling simulations are in accord with experiment. Our calculations suggest that the functional surface of Cn2 and Css4 is primarily formed by the loop between positions 8 and 18, centered on the two charged residues Lys13 and Glu15.
