Nugent, T; Jones, DT; (2010) Predicting Transmembrane Helix Packing Arrangements using Residue Contacts and a Force-Directed Algorithm. PLoS Computational Biology , 6 (3) , Article e1000714. 10.1371/journal.pcbi.1000714.
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Alpha-helical transmembrane proteins constitute roughly 30% of a typical genome and are involved in a wide variety of important biological processes including cell signalling, transport of membrane-impermeable molecules and cell recognition. Despite significant efforts to predict transmembrane protein topology, comparatively little attention has been directed toward developing a method to pack the helices together. Here, we present a novel approach to predict lipid exposure, residue contacts, helix-helix interactions and finally the optimal helical packing arrangement of transmembrane proteins. Using molecular dynamics data, we have trained and cross-validated a support vector machine (SVM) classifier to predict per residue lipid exposure with 69% accuracy. This information is combined with additional features to train a second SVM to predict residue contacts which are then used to determine helix-helix interaction with up to 65% accuracy under stringent cross-validation on a non-redundant test set. Our method is also able to discriminate native from decoy helical packing arrangements with up to 70% accuracy. Finally, we employ a force-directed algorithm to construct the optimal helical packing arrangement which demonstrates success for proteins containing up to 13 transmembrane helices. This software is freely available as source code from http://bioinf.cs.ucl.ac.uk/memsat/mempack/.
|Title:||Predicting Transmembrane Helix Packing Arrangements using Residue Contacts and a Force-Directed Algorithm|
|Open access status:||An open access version is available from UCL Discovery|
|Additional information:||© 2010 Nugent, Jones. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Keywords:||PROTEIN-STRUCTURE PREDICTION, POLYTOPIC MEMBRANE-PROTEINS, SUPPORT VECTOR MACHINES, TOPOLOGY PREDICTION, DATABASE, INFORMATION, ALIGNMENTS, RESTRAINTS|
|UCL classification:||UCL > School of BEAMS > Faculty of Engineering Science > Computer Science|
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