Classification of voltage-gated K+ ion channels from 3D pseudo-folding graph representation of protein sequences using genetic algorithm-optimized support vector machines

Voltage-gated K+ ion channels (VKCs) are membrane proteins that regulate the passage of potassium ions through membranes. This work reports a classification scheme of VKCs according to the signs of three electrophysiological variables: activation threshold voltage (V,), half-activation voltage (V-a50) and half-inactivation voltage (V-h50). A novel 3D pseudo-folding graph representation of protein sequences encoded the VKC sequences. Amino acid pseudo-folding 3D distances count (AAp3DC) descriptors, calculated from the Euclidean distances matrices (EDMs) were tested for building the classifiers. Genetic algorithm (GA)-optimized support vector machines (SVMs) with a radial basis function (RBF) kernel well discriminated between VKCs having negative and positive/zero V-t, V-a50 and V-h50 values with overall accuracies about 80, 90 and 86%, respectively, in crossvalidation test. We found contributions of the "pseudo-core" and "pseudo-surface" of the 3D pseudo-folded proteins to the discrimination between VKCs according to the three electrophysiological variables. (C) 2008 Elsevier Inc. All rights reserved.