Scorpion toxins prefer salt solutions.

There is a wide variety of ion channel types with various types of blockers, making research in this field very complicated. To reduce this complexity, it is essential to study ion channels and their blockers independently. Scorpion toxins, a major class of blockers, are charged short peptides with high affinities for potassium channels. Their high selectivity and inhibitory properties make them an important pharmacological tool for treating autoimmune or nervous system disorders. Scorpion toxins typically have highly charged surfaces and-like other proteins-an intrinsic ability to bind ions (Friedman J Phys Chem B 115(29):9213-9223, 1996; Baldwin Biophys J 71(4):2056-2063, 1996; Vrbka et al. Proc Natl Acad Sci USA 103(42):15440-15444, 2006a; Vrbka et al. J Phys Chem B 110(13):7036-43, 2006b). Thus, their effects on potassium channels are usually investigated in various ionic solutions. In this work, computer simulations of protein structures were performed to analyze the structural properties of the key residues (i.e., those that are presumably involved in contact with the surfaces of the ion channels) of 12 scorpion toxins. The presence of the two most physiologically abundant cations, Na(+) and K(+), was considered. The results indicated that the ion-binding properties of the toxin residues vary. Overall, all of the investigated toxins had more stable structures in ionic solutions than in water. We found that both the number and length of elements in the secondary structure varied depending on the ionic solution used (i.e., in the presence of NaCl or KCl). This study revealed that the ionic solution should be chosen carefully before performing experiments on these toxins. Similarly, the influence of these ions should be taken into consideration in the design of toxin-based pharmaceuticals.