Quantitative parameters for amino acid-base interaction: Implications for prediction of protein-DNA binding sites

Yael Mandel-Gutfreund, Hanah Margalit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

134 Scopus citations


Inspection of the amino acid-base interactions in protein-DNA complexes is essential to the understanding of specific recognition of DNA target sites by regulatory proteins. The accumulation of information on protein-DNA co-crystals challenges the derivation of quantitative parameters for amino acid-base interaction based on these data. Here we use the coordinates of 53 solved protein-DNA complexes to extract all non-homologous pairs of amino acid-base that are in close contact, including hydrogen bonds and hydrophobic interactions. By comparing the frequency distribution of the different pairs to a theoretical distribution and calculating the log odds, a quantitative measure that expresses the likelihood of interaction for each pair of amino acid-base could be extracted. A score that reflects the compatibility between a protein and its DNA target can be calculated by summing up the individual measures of the pairs of amino acid-base involved in the complex, assuming additivity in their contributions to binding. This score enables ranking of different DNA binding sites given a protein binding site and vice versa and can be used in molecular design protocols. We demonstrate its validity by comparing the predictions using this score with experimental binding results of sequence variants of zif268 zinc fingers and their DNA binding sites.

Original languageAmerican English
Pages (from-to)2306-2312
Number of pages7
JournalNucleic Acids Research
Issue number10
StatePublished - 15 May 1998

Bibliographical note

Funding Information:
We thank Robert Jernigan, Victor Zhurkin and Ora Schueler for helpful discussions. This study was supported by a grant to H.M. from the Israel Science Foundation, administered by the Israeli Academy of Sciences and Humanities.


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