Free energy calculation on base specificity of drug – DNA interactions: Application to daunomycin and acridine intercalation into DNA

Abstract
We present the results of free energy perturbation/molecular dynamics studies on B-DNA · daunomycin and B-DNA · 9-aminoacridine complexes as well as on B-DNA itself in order to calculate the free energy differences between complexes having different base pair sequences. The results generally reproduce the trends observed experimentally, i.e., preferences of acridine and daunomycin to bind to a specific base sequence in the DNA. This is encouraging, given the simplicity of the molecular mechanical/dynamical model in which solvent is not explicitly included.