Calculation of the binding affinity of the anticancer drug daunomycin to DNA by a statistical mechanics approach

Equilibrium binding constants of the anticancer drug daunomycin, bound to several GC containing polymeric DNAs (G represent guanine and C cytosine), are calculated by means of a microscopic statistical mechanics approach and based on observed x-ray crystal structures. Our calculation shows base sequence specificity of daunomycin in agreement with the observations. We find the drug binding constant to be sensitive to the base composition of the host sequence. The binding stability decreases in the order of CGTACG, CGATCG, and CGGCCG, which is consistent with observations (T represents thymine and A adenine). This binding specificity arises from sequence specific hydrogen bond and nonbonded interactions between the drug and a host DNA. These interactions are affected by sequence specific structural features exhibited from x-ray crystallography. The agreement between our calculations and experiments shows that our method is of practical application in analyzing sequence specific binding stability of anticancer drugs.