Calculation of the dynamics of drug binding in a netropsin-DNA complex

We calculate the drug binding constant and thermal fluctuational base pair opening probabilities of a netropsin-bound DNA polymer poly d(GATATC)⋅poly d(GATATC) at room temperature (293 K). For comparison we also calculate the probabilities for the free DNA helix. The calculation is carried out by a statistical approach using microscopic structure and established dynamic force fields. The analysis of netropsin binding or dissociation involves calculations of the disruption of several different elements that bind the drug to the DNA helix including hydrogen bonding, the nonbonded attraction in the minor groove, and a conformational factor. Good agreement between our calculated and the observed drug binding constant occurs for a reasonable choice of H-bond parameters for the complex in a solution. Our calculation also shows that the opening probability of the base pairs near the binding site is significantly reduced by a variety of interactions between the helix and the drug.