Indirect Readout in Drug-DNA Complexes

The gene expression control by DNA-binding drugs is of great interest in molecular biology and biotechnology. The ability of some drugs to switch on or off the gene expression brings the possibility to develop treatments for genetic diseases, infection by antibiotic-resistant bacteria, or cancer. The analysis of the DNA sequence-dependent conformational energy gives hints for the design of DNAbinding drugs that modify the DNA conformational state. To accomplish such analysis we used the analogy with the analysis of sequence-dependent DNA conformation for indirect readout mechanism in protein-DNA recognition. The change in intra-molecular conformational energy of DNA upon a complex formation will determine the sequence specificity. Similarly, as the protein indirect readout may result from the recognition of intrinsic conformation of DNA by proteins and/or deformability of DNA upon a complex formation, a drug may use indirect readout to bind to a specific sequence.