Exposure of DNA to UV-light (260-320 nm) leads to the formation of two major photolesions between adjacent pyrimidine nucleobases, the cyclobutane pyrimidine dimer (CPD) and the (6-4) photoproduct (6-4PP). Both originate from an ultrafast [2 + 2] cycloaddition and the process leads to the covalent linking between the two bases. This damage produces stalling of DNA replication and transcription and causes errors in the genome leading to phenotypic display of skin cancer. Many species contain enzymes capable of repairing these photolesions, however, humans do not and must rely on nucleotide excision repair to replace the bases. DNA photolyase is an enzyme capable of binding to and repairing CPD photolesions. A redox active flavin cofactor (FADH-) found near the active site is capable of donating an electron into the CPD breaking orbital symmetry and leading to a breaking of the cyclobutane ring covalently linking the two bases. This repair mechanism is light dependant and highly efficient. As humans do not possess this enzyme, there is much interest in developing small molecules which can mimic DNA photolyase. Our group has developed an artificial photolyase which is capable to binding to CPDs in water effecting repair. The work here builds upon previous studies by testing this artificial photolyase on duplex DNA. (6-4) photolyase is an enzyme capable of repairing the 6-4PP. In contrast to the mechanism of CPD repair, little is known about mechanism employed by (6-4) photolyase. Much debate exists in the literature on what this mechanism is, however, each proposed mechanism is lacking in experimental evidence and support. In this work we use high level electronic structure methods to study the energetic landscape of the proposed mechanisms both in solution and in the (6-4) photolyase active site. By using these methods we conclude that none of the currently proposed mechanisms are energetically feasible and a new, two proton repair mechanism is proposed for the repair of 6-4PP. Much work has been done by scientists in modifying the nucleic backbone of nucleic acids. However, only a few unnatural nucleic acids are known to form stable duplexes. The newly discovered glycol nucleic acid (GNA) is perhaps the simplest backbone scheme capable of duplex formation. It consists of a phosphodiester backbone connected by repeating propylene glycol subunits and is completely acyclic. GNA forms duplexes far exceeding the thermal stabilities of DNA with melting temperatures Ì¢"¡è 20ÌÜ ÁC greater. Thermodynamic analysis shows that GNA duplex formation is entropically less penalizing than the same process in DNA and RNA. This is a counterintuitive notion considering the acyclic nature of the GNA backbone. This study uses molecular dynamics (MD) simulations to study the structure and dynamics of dsGNA and uncovers a coiling/ uncoiling mode which explains the decreased entropic penalty of annealing in comparison to natural nucleic acids. MD simulations are also used to study the arrangement of porphyrin base pairs incorporated into GNA and support the notion of a slipped cofacial geometry of adjacent porphyrin moieties which has been speculated from the experimental data.