Zinc finger proteins, the largest single class of metalloproteins in the human genome, regulate gene transcription and, therefore, protein expression, by site-specific binding to DNA and RNA. Our long-term goal is to improve the rational design of artificial ZFP therapeutics by characterizing the fundamental thermodynamics of their interactions with Zn(II) metal-ions and DNA. Our operating premise is that a complete thermodynamic understanding of Zn(II)-ZFP and ZFP-DNA interactions will provide important insight into the thermodynamic and kinetic mechanisms of selective gene transcription by ZFPs. Understanding both the thermodynamic and kinetic determinants of ZFP transcription factor selectivity will facilitate more intelligent design of ZFP-based therapeutics for heart disease and cancer.

This research is funded by the National Institutes of Health (1SC3GM089634).