Isoelectric point optimization using peptide descriptors and support vector machines

IPG (Immobilized pH Gradient) based separations are frequently used as the first step in shotgun proteomics methods; it yields an increase in both the dynamic range and resolution of peptide separation prior to the LC-MS analysis. Experimental isoelectric point (pI) values can improve peptide identifications in conjunction with MS/MS information. Thus, accurate estimation of the pI value based on the amino acid sequence becomes critical to perform these kinds of experiments. Nowadays, pI is commonly predicted using the charge-state model [1], and/or the cofactor algorithm [2]. However, none of these methods is capable of calculating the pI value for basic peptides accurately. In this manuscript, we present an new approach that can significant improve the pI estimation, by using Support Vector Machines (SVM)[3], an experimental amino acid descriptor taken from the AAIndex database [4] and the isoelectric point predicted by the charge-state model. Our results have shown a strong correlation (R-2=0.98) between the predicted and observed values, with a standard deviation of 0.32 pH units across the complete pH range. (C) 2012 Elsevier B.V. All rights reserved.