Molecular Basis of the Effects of Hydrostatic Pressure on Protein Stability

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professor George Makhatadze of Rensselaer Polytechnic Instiute to investigate the role of various physical-chemical interactions in determining the pressure dependence of protein stability. Pressure is an important environmental variable that plays an essential role in biological adaptation for many extremophilic organisms, called barophiles. This research project will rely upon the synergy between computer simulations and experiments. Computer simulations will provide solid theoretical framework for the analysis of the volume changes upon protein unfolding. Experiments will be performed to validate the computer simulations. In particular, these workers will be testing a hypothesis that proteins from barophilic organisms have volumetric properties that allow them to remain folded, even at elevated hydrostatic pressure. This project engages high school, undergraduate and graduate students in both computational and experimental aspects of the research in the laboratory. In recruiting trainees, there will be a particular effort to engage women and/or members of underrepresented minorities. The PI is also actively involved in curriculum development and serves as an undergraduate curriculum adviser for Biochemistry and Biophysics majors at Rensselaer Polytechnic Institute. The proposed work will provide a significant refinement of a protein stability model to incorporate temperature dependencies of volume changes by combining concepts of evolutionary biology with biochemical and biophysical tools such as nuclear magnetic resonance, differential scanning calorimetry as well as computational tools. It is expected that the knowledge accumulated as a result of these experiments will lay the foundation to understand the factors that affect protein folding and stability under extreme conditions. In the longer term, it is hoped that the lessons learned here will provide biophysical chemists with new insights as they seek to design enzymes with that are both active and robust. Broader scientific impacts in industrial biotechnology and in process chemsitry are anticipated, particularly as these scientists seek to develop robust biomaterials and replace current processes with next generation, environmentally friendly catalytic processes.