Engineering DNA Computation with Unnatural Nucleotides and Protein Function with Unnatural Amino Acids

Synthetic engineering methods, such as DNA computation and unnatural amino acid mutagenesis, have provided a route to improve the control of DNA and proteins. DNA computation encompasses a broad field that attempts to build computational devices from DNA structures. Logic gates are a fundamental component of any larger computational network, and have been constructed from purely DNA frameworks. Operation is determined by strict rules, which allow for the predictable creation of complex circuits. Described herein are methods to alter DNA logic gates with photochemical caging groups, interface logic gates with protein output, and optically control DNA amplification cycles. These methods have enabled precise temporal and spatial control, as well as merged the interface between DNA circuits and biological systems. Unnatural amino acid mutagenesis enables the site specific alteration of protein residues, through the insertion of a non-canonical amino acid. Incorporation of these unnatural residues has greatly expanded the function of proteins, with the introduction of new chemical functionalities. These chemical handles have enabled applications such as the study of abasic bypass in DNA polymerases and protein-RNA crosslinking