Computational Analysis of Membrane Protein Structure .doc

Analysis and prediction of membrane protein structure Tina A. Eyre1, Linda Partridge1 and Janet M. Thornton2 1. Department of Biology, University College London, Darwin Building, Gower Street, London, UK 2. European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK Article number: g406113 Corresponding author: Tina Eyre Please contact me by email or phone where possible. If a fax is necessary, please advise me when it is sent so that I know to collect it. Thanks. Keywords: Transmembrane helix, membrane, membrane protein, structure analysis, structure prediction. Pages: 26 Figures: 6 (5 black/white, 1 colour) Tables: 0  Abstract Despite the importance of membrane proteins, relatively little is known even now about their structures due to the practical difficulties associated with the crystallisation of these proteins. Whilst we can identify transmembrane helices and predict their topology with high accuracy, we do not fully understand the forces which drive the packing of these helices in 3D. Recently, however, more membrane protein structures have become available and several computational studies have analysed them. This chapter describes the results of these analyses and their implications for the prediction of 3D structural models for membrane proteins.  Introduction Transmembrane (TM) proteins are those that span the membrane lipid bilayer and they are estimated to comprise 20-50% of most genomes (Arkin et al., 1997, Wallin and von Heijne., 1998). They are of great biological significance since they mediate most of the communication between cells and cellular compartments and contain many potential drug targets. Despite their abundance and importance, difficulties in the practical approaches to TM protein structure determination have led to few crystal structures being solved until recently. As a result, compared to water-soluble proteins, little is known about the structure of membrane proteins and, even today, only a