Functional classification of membrane transporters and channels based on filtered TM/non-TM amino acid composition

Membrane transporters catalyze the transport of small solute molecules across biological barriers such as lipid bilayer membranes. As the experimental annotation of which proteins transport which substrates is incomplete it is highly desirable to develop computational methods that can assist in the classification and substrate annotation of putative membrane transport proteins. Here, we determined the similarity of membrane transporter sequences annotated in the Transport Classification Database (Saier et al., Nucleic Acids Res 2006, 34, D181-D186) and Arabidopsis thaliana membrane transporters annotated in the database Aramemnon (Schwacke et al., Plant Physiol 2003, 131, 16-26). The similarity measure was based on the amino acid composition either considering the full sequences or separately in the transmembrane (TM) and external parts of the sequences. We considered four different substrate sets and three different subfamilies and tried to classify the given proteins into these classes. Family or substrate prediction based on the simple amino acid frequency had an average accuracy of 76%. The differentiation between TM and non-TM regions led to an improved accuracy of 80% on average.