![]() ![]() This disparity is not due to importance: the location of membrane proteins on the surface of cells and their involvement in signalling pathways make them targets for approximately one-half of current and future drugs ( Overington et al., 2006). For comparison, in July 2012 there were >45 000 unique crystal structures in the Protein Data Bank ( Berman et al., 2000). There are only ∼350 unique membrane protein crystal structures ( ). Alignments generated by MP-T also lead to significantly better models than those of the best alternative alignment tool (one-fourth of models see an increase in GDT_TS of ≥4%).Īvailability: All source code, alignments and models are available at Ĭontact: information: Supplementary data are available at Bioinformatics online. MP-T produces more accurate alignments than all other methods tested (δ F M from +0.9 to +5.5%). ![]() Alignment accuracy is tested against seven other alignment methods over 165 non-redundant alignments of membrane proteins. ![]() Results: We developed Membrane Protein Threader (MP-T), a sequence-structure alignment tool for membrane proteins based on multiple sequence alignment. Here we include these factors into an alignment method to improve alignments and consequently improve membrane protein models. Biological membranes have layers of varying hydrophobicity, and membrane proteins have different amino-acid substitution preferences from their soluble counterparts. This alignment is usually made with programs designed for use on soluble proteins. Models of membrane proteins are typically built from template structures with low sequence identity to the target sequence, using a sequence-structure alignment as a blueprint. Motivation: Membrane proteins are clinically relevant, yet their crystal structures are rare. ![]()
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