Detailed Folding Structures of Kappa-conotoxin RIIIJ and Its Mutageneses Obtained from 2-Dimensional HP Model

Shaomin      Yan; Guang      Wu

doi:10.2174/092986612800190982

Abstract

Kappa-conotoxin RIIIJ is a conopeptide to inhibit voltage-gated potassium channels, however, its detailed folding structures have yet to be studied. With the advance in computing power, it is possible to use the HP model to analyze all its possible folding structures. In this study, the amino acid sequences of kappa-conotoxin RIIIJ and its four mutageneses were converted into ten HP sequences according to the normalized hydrophobicity index. All 282 429 536 481 possible folding structures in each HP sequence were found using the 2-dimensional HP model, and the detailed folding structures at native state were studied. The results showed that kappa-conotoxin RIIIJ had 180 and 90 folding structures at their native state with minimal energy of –9 and –10 at pH 2 and pH 7; its mutagenesis (6-8) TPP -> SLN increased the numbers of the folding structures to 456 and 564 at pH 2 and pH 7; whereas its mutageneses (6-11) TPPKKH -> SLNLRL, (9- 11) KKH -> LRL, and (10-11) KH -> RL decreased the numbers of the folding structures to 60, 30 and 90 at both pH levels, respectively. Thereafter, the normalized hydrophobicity index was employed to distinguish those native states, and attempts were made to explain the effect of mutageneses on potassium channels in terms of the number of folding structures and numerical native states.

Keywords: Folding structure, HP model, Kappa-conotoxin, Minimal energy, Mutagenesis, Native state

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