QUANTITATIVE PARAMETERS FOR AMINO ACID-BASE INTERACTION - IMPLICATIONS FOR PREDICTION OF PROTEIN-DNA BINDING-SITES

Inspection of the amino acid-base interactions in protein-DNA complexe s is essential to the understanding of specific recognition of DNA tar get sites by regulatory proteins. The accumulation of information on p rotein-DNA co-crystals challenges the derivation of quantitative param eters 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, includi ng hydrogen bonds and hydrophobic interactions. By comparing the frequ ency distribution of the different pairs to a theoretical distribution and calculating the log odds, a quantitative measure that expresses t he 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 meas ures of the pairs of amino acid-base involved in the complex, assuming additivity in their contributions to binding. This score enables rank ing of different DNA binding sites given a protein binding site and vi ce verse and can be used in molecular design protocols. We demonstrate its validity by comparing the predictions using this score with exper imental binding results of sequence variants of zif268 zinc fingers an d their DNA binding sites.