DNA Springs Coupled to Proteins

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This award by the Biomaterials program in the Division of Materials Research to University of California Los Angeles is to build a fundamental understanding of the mechanochemistry of proteins and to calibrate the forces produced by DNA oligomers. The biological cell is a miniature chemical factory operated by molecular daemons called enzymes. Each daemon may speed up a specific chemical reaction enormously. The objective of this project is to learn how to control the daemons mechanically, ultimately achieving mechanical control of chemical reactions. Specifically, the project will use a ?molecular spring? to stress the enzyme, and measure the effect on the chemical reaction controlled by that enzyme. This study brings mechanical tools such as springs and levers to bear at the molecular scale, opening a new nanotechnology direction. Scientifically, it will build up our knowledge of the mechano-chemistry of enzymes. Several graduate students and one postdoctoral fellow will be trained in the experimental and theoretical methods of this emerging field, which cuts across disciplines from physics to chemistry to molecular biology and thus offers optimal opportunities to broaden the scientific outlook of young researchers. This research also provides a splendid opportunity to educate the public in these exciting developments in modern science, through public lectures, interactions with LA area teachers (through the facilities of California NanoSystem Institute), and web-based dissemination of important results. Enzymes as biological catalysts, couple mechanical motion and forces to chemical reactions through conformational transitions. Moving beyond structural descriptions, the objective of this project is to build a dynamic understanding of these complex structures, in terms of the elastic energies and forces which couple to the chemistry. Through a unique method which uses DNA as "molecular springs" attached to the enzyme, the investigators will apply controlled mechanical stresses to several proteins and measure the effect on the different steps which determine the reaction rate. Parallel experiments will answer the longstanding question of what is the elastic energy of sharply bent configurations of DNA, in other words, will calibrate the DNA springs. The knowledge will be applied to the parametrization of nonlinear models of DNA mechanics. This research explores fundamental physics at the boundary of chemistry and mechanics. It provides the vehicle for training graduate students and postdoctoral fellows in paradigm-changing biological physics research, both experimental and theoretical.