This work focuses on the binding of a model intercalant (indole) between the ten possible pairings of the four DNA bases [Adenine, Cytosine, Guanine, and Thymine; parings include: AIA, AIG, AIT, CIC, CIA, CIG, CIT, GIG, GIT, and TIT] in order to ascertain the most likely location of the binding of a carcinogen or chemotherapeutic drug in between the DNA. This knowledge will aid in the design and targeting of future chemotherapy drugs. Each of the ten complexes (DNA base-intercalant-DNA base) was optimized into both the open, t-shaped structure and the parallel sandwich structure using MP2/6-31g, yielding twenty total structures. Interaction energies were computed for all twenty of these complexes using MP2 as well as several DFT methods with the 6-31+g* and 6-311+g* basis sets. Comparison of the stability of the open, t-shaped structures to the stability of the sandwich structures, allowed estimation of the distorting force acting on that segment of DNA. A short strand of DNA with an intercalant bound in between two bases corresponding to each of the complexes mentioned above was then studied using the ONIOM method. For these calculations, MP2 and DFT methods were used to model the interactions between the bases and the intercalant, while AM1 was used to model the DNA backbone. These calculations that include large segments of DNA strands are crucial to this study because the manner in which DNA distorts depends heavily on the backbone and the presence of the neighboring DNA bases. Finally, models of the intercalant bound between pairs of two bases in double stranded DNA were modeled using ONIOM. By comparing the results from the free, the single stranded, and double stranded models, the importance of the environment to the binding of an intercalant in DNA can be shown.

Increasingly complex models for intercalation of a planar molecule between DNA bases: MP2, DFT, and ONIOM results

241st National Meeting (2011)

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