Aims

• To introduce bioinformatics challenges in predicting the structures of membrane proteins.

Objectives

After this lecture you will:

• be aware of computational approaches to predicting the transmembrane regions of membrane proteins, and their topology;
• be aware of issues and challenges in predicting the packing of transmembrane helices.

Supplementary Material

The lecture handout is available on-line (local access).

The method used in the TMHMM program is described in:

Sonnhammer, E.L.L., von Heijne, G. and Krogh, A. (1998) "A Hidden Markov Model for Predicting Transmembrane Helices in Protein Sequences", Proceedings of ISMB 6, pp 175-182 (available from Erik Sonnhammer's publications page)

Several methods for predicting membrane spanning regions are evaluated in:

Möller, S., Croning, M.D. and Apweiler, R. (2001) "Evaluation of methods for the prediction of membrane spanning regions", Bioinformatics, 17, 646-653 (PubMed)

Approaches to modelling the transmembrane domain of phospholamban are described in:

Adams, P.D., Arkin, I.T., Engelman, D.M. and Brünger, A.T. (1995) "Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban", Nat Struct Biol., 2, 154-162 (available from Axel Brünger's publications page)

Herzyk, P., Hubbard, R.E. (1998) "Using experimental information to produce a model of the transmembrane domain of the ion channel phospholamban" Biophys J., 74, 1203-1214 (PubMed)

A minireview of the GPCR modelling field is presented in:

Oliveira, L., Hulsen, T., Lutju Hulsik, D., Paiva, A.C.M. and Vriend, G.(2004) Heavier-than-air flying machines are impossible. FEBS Lett., 564, 269-273 (PubMed)

An interesting hypothesis for occurence of transmembrane helix kinks is proposed in:

Yohannan, S., Faham, S., Yang, D., Whitelegge, J.P., and Bowie, J.U. (2004) The evolution of transmembrane helix kinks and the structural diversity of G protein-coupled receptors. Proc Natl Acad Sci USA, 101, 959-963 (PubMed)