Photoacoustic Instrument for Protein Folding

The instrument we refer to as "Big Bang" uses a moderately powered laser flash to initiate therelease of photolabile "caged" groups such as protons, which then will induce conformational changesin a biological polymer such as a protein or DNA. The conformational changes of the polymer will induceacoustic waves within the solution resulting from phenomena such as changes in partial specific volume,electrostriction or changes in solvation. A piezoelectric transducer will detect the acoustic pressurewaves (i.e. "listen" to the ultrasound generated), and deconvolution techniques will be used to analyzethe kinetics of the resulting conformational change. Optical methods, including Rayleigh light scattering,will also be used to monitor conformational changes. With access to the nanosecond and microsecondtime scales, this instrument will be orders of magnitude faster than traditional stopped flow techniqueswhich typically have mixing times on the order of a millisecond. It should also be less expensive to build.We expect this instrument to find large markets in biotechnology research and industry, particularly instudies involving protein folding. We will build a prototype of this instrument and test the feasibility ofthis approach for measuring helix-coil transitions in a model protein system, poly-L-glutamate.