Orientations of Proteins in Membranes: Tools and Database

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

The University of Michigan in Ann Arbor has received a grant to develop computational tools and a database for structural studies, modeling and comparative analysis of membrane-associated peptides and proteins. More than half of all proteins in cells interact with membranes. These proteins do not function individually but as large multi-protein complexes immersed in the phospholipid matrix. Although many individual components of biological membranes are well studied at the atomic level, little is known about the spatial organization and the function of membranes as supra-molecular assemblies. In particular, the spatial positions in the lipid bilayer have been experimentally studied only for a few dozen out of several thousands of membrane-associated proteins deposited in the Protein Data Bank (PDB). To fill this gap, a fast computational method to determine the optimal rotational and translational positions of proteins in membranes has recently been developed. This method will be extended, improved and adapted for the automated large-scale analysis of membrane-associated proteins from the PDB and for modeling alpha-helical domains of single-spanning transmembrane proteins. The computational tools will include software for positioning proteins in membranes (PPM 2.0) and folding of membrane-associated peptides (FMAP), as well as the next generation of the Orientations of Proteins in Membranes (OPM) database (http://opm.phar.umich.edu). The expanded OPM database will hold several thousand three-dimensional structures of transmembrane and peripheral peptides and proteins. It will provide the calculated spatial positions of the proteins with respect to the lipid bilayer, classification of membrane proteins into evolutionarily related families, along with their subcellular localization, topology, biological source, functional data, interactive visualization tools and links to other bioinformatics resources. These tools and the expanded database will satisfy the needs of researchers who work in the field of membrane proteomics, lipidomics, biophysics, biochemistry and cell biology. They are vital for the comparative evolutionary analysis, experimental mutagenesis studies and de novo design of membrane peptides and proteins. The planned resources will also be very valuable for teaching and will enhance the Medicinal Chemistry and bioinformatics curriculum at University of Michigan and other schools worldwide. The graphical representation of data and visualization tools will be especially useful for teaching high school and undergraduate college students, as well as for the general public.