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De novo prediction of DNA-binding specificities for Cys2His2zinc finger proteins

Author(s): Persikov, AV; Singh, Mona

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Abstract: Proteins with sequence-specific DNA binding function are important for a wide range of biological activities. De novo prediction of their DNA-binding specificities from sequence alone would be a great aid in inferring cellular networks. Here we introduce a method for predicting DNA-binding specificities for Cys2His2 zinc fingers (C2H2-ZFs), the largest family of DNA-binding proteins in metazoans. We develop a general approach, based on empirical calculations of pairwise amino acid–nucleotide interaction energies, for predicting position weight matrices (PWMs) representing DNA-binding specificities for C2H2-ZF proteins. We predict DNA-binding specificities on a per-finger basis and merge predictions for C2H2-ZF domains that are arrayed within sequences. We test our approach on a diverse set of natural C2H2-ZF proteins with known binding specificities and demonstrate that for >85% of the proteins, their predicted PWMs are accurate in 50% of their nucleotide positions. For proteins with several zinc finger isoforms, we show via case studies that this level of accuracy enables us to match isoforms with their known DNA-binding specificities. A web server for predicting a PWM given a protein containing C2H2-ZF domains is available online at and can be used to aid in protein engineering applications and in genome-wide searches for transcription factor targets.
Publication Date: 1-Jan-2014
Electronic Publication Date: 3-Oct-2013
Citation: Persikov, AV, Singh, M. (2014). De novo prediction of DNA-binding specificities for Cys<inf>2</inf>His<inf>2</inf>zinc finger proteins. Nucleic Acids Research, 42 (97 - 108. doi:10.1093/nar/gkt890
DOI: doi:10.1093/nar/gkt890
Pages: 97 - 108
Type of Material: Journal Article
Journal/Proceeding Title: Nucleic Acids Research
Version: Final published version. This is an open access article.

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