ABSTRACT
We have presented several methods for monitoring the interactions of toxicants with dsDNA based on DNA biosensors. These methods can aid in assessing the damage and structural modifi cations caused to dsDNA by herbicides and pesticides and are suitable for screening of a wide range of herbicides and pesticides in different formulations and with different adjuvants. In particular, we have demonstrated that simple techniques with a variety of signal transduction schemes can be applied for detecting DNA alterations due to the herbicide interactions with DNA including intercalation to a DNA double-helix. On the basis of experimental results and with the help of MD simulations and QM calculations it becomes possible to evaluate the extent of dsDNA damage and possible weak spots in the double-helix structure. The weakest spots in DNA sequences are those with multiple TA base-pairs where unwinding is energetically favored because of the weakness in the strained hydrogen bonding there. Also, the base stacking interactions between T-T, T-A, and A-A bases are the weakest among other combinations of base stackings. Small molecules, like atrazine, fi t neatly in the space between the stacked bases disrupting the local inter-helix hydrogen bonding and changing the DNA conformation because of the expansion of the inter-base distance in one side of a doublehelix. This happens since the intercalator molecule is too small to match the entire base-pair in DNA.
