Co-evolving residues in membrane proteins

@article{citeulike:2076381, abstract = {Motivation: The analysis of co-evolving residues has been exhaustively evaluated for the prediction of intramolecular amino acid contacts in soluble proteins. Although a variety of different methods for the detection of these co-evolving residues have been developed, the fraction of correctly predicted contacts remained insufficient for their reliable application in the construction of structural models. Membrane proteins, which constitute between one-fourth and one-third of all proteins in an organism, were only considered in few individual case studies. Results: We present the first general study of correlated mutations in {alpha}-helical membrane proteins. Using seven different prediction algorithms, we extracted co-evolving residues for 14 membrane proteins having a solved 3D structure. On average, distances between correlated pairs of residues lying on different transmembrane segments were found to be significantly smaller compared to a random prediction. Covariation of residues was frequently found in direct sequence neighborhood to helixhelix contacts. Based on the results obtained from individual prediction methods, we constructed a consensus prediction for every protein in the dataset that combines obtained correlations from different prediction algorithms and simultaneously removes likely false positives. Using this consensus prediction, 53\% of all predicted residue pairs were found within one helix turn of an observed helixhelix contact. Based on the combination of co-evolving residues detected with the four best prediction algorithms, interacting helices could be predicted with a specificity of 83\% and sensitivity of 42\%. Availability: http://webclu.bio.wzw.tum.de/helixcorr/ Contact: d.frishman@wzw.tum.de Supplementary information: Supplementary data are available at Bioinformatics online. 10.1093/bioinformatics/btm515}, author = {Fuchs, Angelika and Martin-Galiano, Antonio J. and Kalman, Matan and Fleishman, Sarel and Ben-Tal, Nir and Frishman, Dmitrij }, citeulike-article-id = {2076381}, doi = {10.1093/bioinformatics/btm515}, journal = {Bioinformatics}, keywords = {co-evolution, membrane, protein, residue}, month = {December}, number = {24}, pages = {3312--3319}, posted-at = {2007-12-10 03:52:09}, priority = {3}, title = {Co-evolving residues in membrane proteins}, url = {http://dx.doi.org/10.1093/bioinformatics/btm515}, volume = {23}, year = {2007} }

TY - JOUR ID - citeulike:2076381 L3 - citeulike-article-id:2076381 TI - Co-evolving residues in membrane proteins JF - Bioinformatics VL - 23 IS - 24 SP - 3312 EP - 3319 N2 - Motivation: The analysis of co-evolving residues has been exhaustively evaluated for the prediction of intramolecular amino acid contacts in soluble proteins. Although a variety of different methods for the detection of these co-evolving residues have been developed, the fraction of correctly predicted contacts remained insufficient for their reliable application in the construction of structural models. Membrane proteins, which constitute between one-fourth and one-third of all proteins in an organism, were only considered in few individual case studies. Results: We present the first general study of correlated mutations in {alpha}-helical membrane proteins. Using seven different prediction algorithms, we extracted co-evolving residues for 14 membrane proteins having a solved 3D structure. On average, distances between correlated pairs of residues lying on different transmembrane segments were found to be significantly smaller compared to a random prediction. Covariation of residues was frequently found in direct sequence neighborhood to helixhelix contacts. Based on the results obtained from individual prediction methods, we constructed a consensus prediction for every protein in the dataset that combines obtained correlations from different prediction algorithms and simultaneously removes likely false positives. Using this consensus prediction, 53% of all predicted residue pairs were found within one helix turn of an observed helixhelix contact. Based on the combination of co-evolving residues detected with the four best prediction algorithms, interacting helices could be predicted with a specificity of 83% and sensitivity of 42%. Availability: http://webclu.bio.wzw.tum.de/helixcorr/ Contact: d.frishman@wzw.tum.de Supplementary information: Supplementary data are available at Bioinformatics online. 10.1093/bioinformatics/btm515 KW - co-evolution KW - membrane KW - protein KW - residue AU - Fuchs, Angelika AU - Martin-Galiano, Antonio AU - Kalman, Matan AU - Fleishman, Sarel AU - Ben-Tal, Nir AU - Frishman, Dmitrij PY - 2007/12/15/ UR - http://dx.doi.org/10.1093/bioinformatics/btm515 ER -