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Predicting Transmembrane Helix Packing Arrangements using Residue Contacts and a Force-Directed Algorithm

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. Green and gold open access

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Abstract

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/.

Type:Article
Title:Predicting Transmembrane Helix Packing Arrangements using Residue Contacts and a Force-Directed Algorithm
Open access status:An open access publication. A version is also available from UCL Discovery.
DOI:10.1371/journal.pcbi.1000714
Publisher version:http://dx.doi.org/10.1371/journal.pcbi.1000714
Language:English
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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