Accurate de novo structure prediction of large transmembrane protein domains using fragment-assembly and correlated mutation analysis
- 29 May 2012
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 109 (24) , E1540-7
- https://doi.org/10.1073/pnas.1120036109
Abstract
A new de novo protein structure prediction method for transmembrane proteins (FILM3) is described that is able to accurately predict the structures of large membrane proteins domains using an ensemble of two secondary structure prediction methods to guide fragment selection in combination with a scoring function based solely on correlated mutations detected in multiple sequence alignments. This approach has been validated by generating models for 28 membrane proteins with a diverse range of complex topologies and an average length of over 300 residues with results showing that TM-scores > 0.5 can be achieved in almost every case following refinement using MODELLER. In one of the most impressive results, a model of mitochondrial cytochrome c oxidase polypeptide I was obtained with a TM-score > 0.75 and an rmsd of only 5.7 Å over all 514 residues. These results suggest that FILM3 could be applicable to a wide range of transmembrane proteins of as-yet-unknown 3D structure given sufficient homologous sequences.Keywords
This publication has 54 references indexed in Scilit:
- Direct-coupling analysis of residue coevolution captures native contacts across many protein familiesProceedings of the National Academy of Sciences, 2011
- Protein topology from predicted residue contactsProtein Science, 2011
- MEDELLER: homology-based coordinate generation for membrane proteinsBioinformatics, 2010
- How significant is a protein structure similarity with TM-score = 0.5?Bioinformatics, 2010
- Predicting helix–helix interactions from residue contacts in membrane proteinsBioinformatics, 2009
- Prediction of membrane protein structures with complex topologies using limited constraintsProceedings of the National Academy of Sciences, 2009
- Identification of direct residue contacts in protein–protein interaction by message passingProceedings of the National Academy of Sciences, 2009
- Predicting residue–residue contact maps by a two‐layer, integrated neural‐network methodProteins-Structure Function and Bioinformatics, 2008
- Prediction of membrane-protein topology from first principlesProceedings of the National Academy of Sciences, 2008
- Toward high-resolution prediction and design of transmembrane helical protein structuresProceedings of the National Academy of Sciences, 2007