Letter abstract
Nature Biotechnology 26, 1041 - 1045 (2008)
Published online: 17 August 2008 | Corrected online: 9 October 2008 | doi:10.1038/nbt.1489
There is a Corrigenda (October 2008) associated with this Letter.
There is a Corrigenda (October 2008) associated with this Letter.
Predicting PDZ domain–peptide interactions from primary sequences
Jiunn R Chen1,3,5, Bryan H Chang2,5, John E Allen2, Michael A Stiffler2,4 & Gavin MacBeath2
PDZ domains constitute one of the largest families of interaction domains and function by binding the C termini of their target proteins1, 2. Using Bayesian estimation, we constructed a three-dimensional extension of a position-specific scoring matrix that predicts to which peptides a PDZ domain will bind, given the primary sequences of the PDZ domain and the peptides. The model, which was trained using interaction data from 82 PDZ domains and 93 peptides encoded in the mouse genome3, successfully predicts interactions involving other mouse PDZ domains, as well as PDZ domains from Drosophila melanogaster and, to a lesser extent, PDZ domains from Caenorhabditis elegans. The model also predicts the differential effects of point mutations in peptide ligands on their PDZ domain–binding affinities. Overall, we show that our approach captures, in a single model, the binding selectivity of the PDZ domain family.
- Department of Molecular and Cellular Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
- Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
- Present address: Sloan-Swartz Center for Theoretical Neurobiology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, California 94143, USA.
- Present address: Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Boulevard, Dallas, Texas 75390, USA.
- These authors contributed equally to this work.
Correspondence to: Gavin MacBeath2 e-mail: macbeath@chemistry.harvard.edu
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