Computational Design of Protein-DNA Cleavage Specificity in a Homing Endonuclease

Ashworth J, Havranek JJ, et al. Nature 441, 656-9. (2006)

  High-resolution modeling of protein-DNA interactions has granted us the ability to estimate the specificities of real and hypothetical interfaces. This approach may be useful to design novel sequence-specific endonucleases for biotechnology and medicine.

The figure at left depicts the (crystallographically and biochemically validated) model of a strong switch in the basepair specificity of the endonuclease I-MsoI at a single symmetric position in the recognition region. Generalization of this method may allow us to broadly engineer novel DNA cleavage specificities using computational design.