Hybrid Ab Initio/Empirical Modeling of the Conformations and Light-Induced Transitions in Stilbene-Derivatives Bonded to DNA

Modeling and simulation techniques are presented, which are both physically accurate and computationally efficient for treating complex organic structures that have relevance to sensing and characterization, including structures with covalent bonding to biological (i.e., DNA) molecules. The theoretical study of large and complex biological molecular systems is very challenging because ab initio quantum mechanical methods are usually too computationally demanding and alternative empirical approaches are often insufficient for describing the internal interactions and dynamics. The goal of this research is to provide detailed insight into the molecular interaction mechanisms (e.g., terahertz (THz) frequency spectral absorption), which can be used to define novel types of bioelectronic-sensing devices. Therefore, a mixed ab initio/molecular mechanical-modeling approach is implemented and applied to the study of stilbene-DNA conjugates that offer switchable spectral characteristics that may be useful for detection and identification purposes. In particular, results are generated for two conformations of a TGCGCA-DNA duplex with trimethoxystilbene carboxamide (TMS) end capping that are confirmed by experimental data. The model is also used to derive the influences of DNA sequence and/or TMS orientation on the conformation, electronic states, and atomic vibrations of single- and doubled-stranded variants of the TGCGCA-DNA duplex. These results, which include very distinct absorption spectra in the THz to UV range, demonstrate that hybrid methodologies can bridge the gap in understanding electronic and atomic structure, and light-induced interactions in complex bioorganic systems.