Prediction of transmembrane protein topology

Membrane proteins fulfil many critical cellular functions, and make up a large fraction of all proteins. In fact, it has recently been estimated that as many as 35–-40% of all yeast genes may code for integral membrane proteins (1,2). Yet, only a handful of high resolution membrane protein three-dimensional structures are known, making it even more important to extract as much structural information as possible from the amino acid sequences. This chapter will focus on the topology prediction problem: how to identify transmembrane segments and how to predict the overall orientation of the protein in the membrane.