Multiple alignment of transmembrane protein sequences

Multiple sequence alignment remains one of the most powerful tools for assessing evolutionary sequence relationships and for identifying structurally and functionally important protein regions. Membrane-bound proteins represent a special class of proteins. The regions that insert into the cell membrane have a profoundly different hydrophobicity pattern as compared with soluble proteins. Multiple alignment techniques employing scoring schemes tailored for sequences of soluble proteins are therefore in principle not optimal to align membrane-bound proteins. In this chapter we describe some of the characteristics leading transmembrane proteins to display differences at the sequence level. We will also cover computational strategies and methods developed over the years for aligning this special class of proteins, discuss some current bottlenecks, and suggest some avenues for improvement.