Functional classification of G-Protein coupled receptors, based on their specific ligand coupling patterns

Abstract

Functional identification of G-Protein Coupled Receptors (GPCRs) is one of the current focus areas of pharmaceutical research. Although thousands of GPCR sequences are known, many of them re- main as orphan sequences (the activating ligand is unknown). Therefore, classification methods for automated characterization of orphan GPCRs are imperative. In this study, for predicting Level 2 subfamilies of Amine GPCRs, a novel method for obtaining fixed-length feature vectors, based on the existence of activating ligand specific patterns, has been developed and utilized for a Support Vector Machine (SVM)-based classification. Exploiting the fact that there is a non-promiscuous relationship between the specific binding of GPCRs into their ligands and their functional classification, our method classifies Level 2 subfamilies of Amine GPCRs with a high predictive accuracy of 97.02% in a ten-fold cross validation test. The presented machine learning approach, bridges the gulf between the excess amount of GPCR sequence data and their poor functional characterization.