Structure prediction of membrane proteins

Twenty-five percent of the human genome encodes membrane proteins. Many are related to diseases and their treatments, for example is 30-40% of the top 100 selling drugs world-wide targeted towards G-protein coupled receptors (GPCR). Despite their abundance and importance, only 1% of the known 3D structures are membrane proteins due to experimental difficulties. Integral membrane proteins with determined structures include ion channels,bovine rhodopsin (a GPCR), bacteriorhodopsin, transporters and photosynthetic reaction centra. Each structure has led to important, detailed mechanistic information, and still they represent only a minute fraction of the fold space and functionality of membrane proteins. This fact has stimulated development of membrane proteins structure prediction methods, mainly focussed on GPCRs. There are numerous examples of homology modelling of rhodopsin-like GPCRs using the single high-resolution GPCR structure, that of rhodopsin. Modelling of the other types of GPCRs with low sequence similarity, or of any other integral membrane protein, is however a considerable challenge.

The research aim is to increase the understanding of specific membrane proteins by providing structural models that can explain available data and guide the design of new experiments. A novel protocol for structure prediction of membrane proteins will be devised such that template structures are not needed, and it will therefore be general for any class of helical membrane proteins.

Other projects

Other areas of interest involves homology modeling of membrane and soluble proteins, sequence and structure analysis, protein-protein docking and virtual ligand screening. These tools are used in current collaborations with experimentalists. Feel free to email lars.brive@molbio.gu.se if you have an interesting project that needs bioinformatics support.

Personal

Education

1992-1998 Ph.D, Organic Chemistry, Göteborg University. Thesis title: "NMR spectroscopic studies of structure and function of de novo designed four-helix bundle proteins"; Supervisor Lars Baltzer
1999-2001 Postdoc at the Burnham Institute, La Jolla, USA with Professor Kathryn Ely
2001-2003 Research Associate at the Scripps Research Institute, La Jolla, USA with Professor Ruben Abagyan
2003-2004 Postdoc (repartriation) at the Chemistry Dept, Biophysics at Göteborg University

Position

2004-current Forskarassistent (Assistant Professor) at Molecular Biology, Cell and Molecular Biology, Göteborg University
Created 2004-09-06; Last updated 2004-09-07