ICTX-type: a sequence-based predictor for identifying the types of conotoxins in targeting ion channels.

Hui Ding,Wei Chen,Hao Lin,Lu-Feng Yuan,Kuo-Chen Chou,En-Ze Deng,Li Liu

doi:10.1155/2014/286419

Abstract

Conotoxins are small disulfide-rich neurotoxic peptides, which can bind to ion channels with very high specificity and modulate their activities. Over the last few decades, conotoxins have been the drug candidates for treating chronic pain, epilepsy, spasticity, and cardiovascular diseases. According to their functions and targets, conotoxins are generally categorized into three types: potassium-channel type, sodium-channel type, and calcium-channel types. With the avalanche of peptide sequences generated in the postgenomic age, it is urgent and challenging to develop an automated method for rapidly and accurately identifying the types of conotoxins based on their sequence information alone. To address this challenge, a new predictor, called iCTX-Type, was developed by incorporating the dipeptide occurrence frequencies of a conotoxin sequence into a 400-D (dimensional) general pseudoamino acid composition, followed by the feature optimization procedure to reduce the sample representation from 400-D to 50-D vector. The overall success rate achieved by iCTX-Type via a rigorous cross-validation was over 91%, outperforming its counterpart (RBF network). Besides, iCTX-Type is so far the only predictor in this area with its web-server available, and hence is particularly useful for most experimental scientists to get their desired results without the need to follow the complicated mathematics involved.

Highlights

Being peptides consisting of about 10 to 30 amino acid residues, conotoxins are toxins secreted by cone snails for capturing prey and securing themselves
This kind of toxins can bind to various targets, such as G protein-coupled receptors (GPCRs), nicotinic acetylcholine, and neurotensin receptors
Ion channels represent a class of membrane spanning protein pores that mediate the flux of ions in a variety of cell types

Summary

Introduction

Being peptides consisting of about 10 to 30 amino acid residues, conotoxins are toxins secreted by cone snails for capturing prey and securing themselves This kind of toxins can bind to various targets, such as G protein-coupled receptors (GPCRs), nicotinic acetylcholine, and neurotensin receptors. Ion channel dysfunction may lead to a number of diseases, such as epilepsy, arrhythmia, and type II diabetes These kinds of diseases are primarily treated with the drugs that modulate the ion channels concerned. The following three kinds of ion channels are usually the targets by conotoxins: potassium (K) channel (Figure 1), sodium (Na) channel (Figure 2), and calcium (Ca) channel (Figure 3)

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Conclusion