Memoir: template-based structure prediction for membrane proteins

Jean-Paul Ebejer,Sebastian Kelm,Jamie R Hill,Charlotte M Deane,Jiye Shi

doi:10.1093/nar/gkt331

Jean-Paul Ebejer, Sebastian Kelm + Show 3 more

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https://doi.org/10.1093/nar/gkt331

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Abstract

Membrane proteins are estimated to be the targets of 50% of drugs that are currently in development, yet we have few membrane protein crystal structures. As a result, for a membrane protein of interest, the much-needed structural information usually comes from a homology model. Current homology modelling software is optimized for globular proteins, and ignores the constraints that the membrane is known to place on protein structure. Our Memoir server produces homology models using alignment and coordinate generation software that has been designed specifically for transmembrane proteins. Memoir is easy to use, with the only inputs being a structural template and the sequence that is to be modelled. We provide a video tutorial and a guide to assessing model quality. Supporting data aid manual refinement of the models. These data include a set of alternative conformations for each modelled loop, and a multiple sequence alignment that incorporates the query and template. Memoir works with both α-helical and β-barrel types of membrane proteins and is freely available at http://opig.stats.ox.ac.uk/webapps/memoir.

Highlights

Membrane proteins mediate the exchange of signals and chemicals into every cell
The accuracy of the model is determined by the quality of the alignment between the target and template, and by the coordinate generation method that turns this alignment into a 3D structure
Template protein structures are annotated by the iMembrane program [8]. iMembrane annotates each residue in the structure according to its accessible surface area, secondary structure, membrane positioning and extent of contact with lipids. iMembrane’s

Summary

Introduction

Membrane proteins mediate the exchange of signals and chemicals into every cell. Despite their pharmaceutical importance, few membrane protein crystal structures exist. The MPStruc database (http://blanco.biomol.uci.edu/ mpstruc/) estimates that there are 383 unique protein structures in the protein data bank (PDB; as of 26 January 2013). The PDB itself contains 50 000 unique chains [1], meaning that despite comprising 25% of known sequences [2], membrane proteins constitute

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