Comparative genomics and functional annotation of bacterial transporters

Transport proteins are difficult to study experimentally, and because of that their functional characterization trails that of enzymes. The comparative genomic analysis is a powerful approach to functional annotation of proteins, which makes it possible to utilize the genomic sequence data from thousands of organisms. The use of computational techniques allows one to identify candidate transporters, predict their structure and localization in the membrane, and perform detailed functional annotation, which includes substrate specificity and cellular role. We overview the main techniques of analysis of transporters' structure and function. We consider the most popular algorithms to identify transmembrane segments in protein sequences and to predict topology of multispanning proteins. We describe the main approaches of the comparative genomics, and how they may be applied to the analysis of transporters. and provide examples showing how combinations of these techniques is used for functional annotation of new transporter specificities in known families, characterization of new families, and prediction of novel transport mechanisms. (C) 2007 Elsevier B.V. All rights reserved.