%0 Journal Article %J Bioinformatics %D 2009 %T ModLink+: Improving fold recognition by using protein-protein interactions %A Fornes, O. %A Aragues, R. %A Espadaler, J. %A M. A. Marti-Renom %A Sali, A. %A Oliva, B. %K protein folding %X

MOTIVATION: Several strategies have been developed to predict the fold of a target protein sequence, most of which are based on aligning the target sequence to other sequences of known structure. Previously, we demonstrated that the consideration of protein-protein interactions significantly increases the accuracy of fold assignment compared to PSI-BLAST sequence comparisons. A drawback of our method was the low number of proteins to which a fold could be assigned. Here, we present an improved version of the method that addresses this limitation. We also compare our method to other state-of-the-art fold assignment methodologies. RESULTS: Our approach (ModLink+) has been tested on 3,716 proteins with domain folds classified in the Structural Classification Of Proteins (SCOP) as well as known interacting partners in the Database of Interacting Proteins (DIP). For this test set, the ratio of success (PPV) on fold assignment increases from 75% for PSI-BLAST, 83% for HHSearch and 81% for PRC to more than 90% for ModLink+ at the e-value cutoff of 10(-3). Under this e-value, ModLink+ can assign a fold to 30-45% of the proteins in the test set, while our previous method could cover less than 25%. When applied to 6,384 proteins with unknown fold in the yeast proteome, ModLink+ combined with PSI-BLAST assigns a fold for domains in 3,738 proteins, while PSI-BLAST alone only covers 2,122 proteins, HHSearch 2,969 and PRC 2,826 proteins, using a threshold e-value that would represent a PPV higher than 82% for each method in the test set. AVAILABILITY: The ModLink+ server is freely accessible in the World Wide Web at http://sbi.imim.es/modlink/. CONTACT: boliva@imim.es.

%B Bioinformatics %G eng %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19357100