Structure-Specificity Relationship in Protein-DNA Recognition

Abstract

Regulatory proteins bind to specific DNA sequences and play a critical role in controlling gene expression. However, the mechanism of specific binding is not well understood yet. Structural data on protein—DNA complex provides clues for understanding the mechanism of target DNA sequence recognition by regulatory proteins. Such structures indicate that there is no simple one-to-one correspondence between base and amino acid in protein—DNA complexes. We have, therefore, developed statistical potentials based on the complex structures to quantify the specificity of interactions. Previously, we demonstrated that the potentials successfully discriminated target sequences among random sequences. It is interesting to see if they can detect difference in specificity in symmetric/asymmetric and cognate/non-cognate binding in which subtle structural changes are often observed. We demonstrate how such examples are analyzed by the potentials and discuss how they are different in protein—DNA interaction.