| Protein-DNA interactions are fundamental in biology, evolution, disease, and biotechnology. This dissertation describes the use of state-of-the-art molecular modeling algorithms and supercomputing to more fully understand the molecular details of protein-DNA interfaces, anal to redesign protein-DNA recognition in order to create cutting edge reagents for genomic medicine. Here I show that all-atom physical modeling protocols derived from "first principles" and knowledge-based biophysical properties can recapitulate many native properties of DNA-binding proteins and enzymes, and can be used to rationally design the cleavage specificity of a homing endonuclease at multiple and adjacent base pairs. |
