RUI: Investigating DNA Deformation Induced by Cation Binding Using Computational Analysis of X-ray Crystal Structures

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It is well known that DNA contains the instructions for building live organisms. Less well known is that many of these instructions are not used directly. Which instructions are actually used is partially determined by how the DNA is bent and folded. Therefore, understanding the mechanisms by which DNA is deformed is important to understanding the function of DNA in the storage and expression of genetic information. This project investigates the tendency of cation binding to distort DNA. The experimental focus of the project involves using computational analysis to test the ability of cations to induce two types of DNA deformation: (1) phosphate crowding that occurs in bending and groove narrowing; and (2) base unstacking by ions interacting with base faces via cation-pi interactions. The ability of monovalent cationic protein side chains to induce DNA phosphate crowding in crystal structures of DNA/protein complexes will be analyzed. The project will also characterize cation-pi interactions in DNA by computational analysis of DNA crystal structures as well as determines the crystal structures of DNA complexes with various divalent cations.Broader Impacts: Students engaged in this interdisciplinary research will learn skills important in experimentally determining crystal structures as well as computational skills to analyze structural information available in databases. The projects described herein will develop scientific thinking skills and programming skills that when combined with practical structure determination skills, will give the student well-rounded experience of these symbiotic aspects of structural biology. The students' education will be further expanded by close collaboration with and travel to two major research institutions to collect and analyze crystallographic data.