Coordination Funds

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Pressure acts on the structure and dynamics of biomolecular systems through changes in specific volume that are largely due to changes in hydration or packing efficiency. Thus, high hydrostatic pressure is uniquely well suited for studying the role of solvation in folding, dynamics, and interactions of proteins and other biomolecules. Pressure is also ideal for characterizing spontaneous fluctuations, because fluctuations involve a change in volume, and high-energy conformers that are normally not easily accessible experimentally can be stabilized by pressure. Moreover, the balance between hydrogen bonding, electrostatic and hydrophobic interactions can be changed. In this initiative, we want to focus on a molecular level-based bottom-up description of pressure effects on solutions of biomolecules, and the use of pressure modulation to reveal important mechanistic information on fundamental biomolecular processes and reactions. Grounded on accurate reference investigations of small biomolecules and compatible solutes at high pressure conditions, we are mapping the conformational and functional substates as well as intermolecular interactions of proteins by pressure modulation. Pressure will also be used to reveal information on protein assembly and disassembly and to modulate membrane-assisted processes as well as enzymatic conversions. Finally, invaluable information will be gained on the structural, dynamical and functional properties of proteins under extreme environmental conditions. These studies will couple a number of sensitive and powerful biophysical techniques, including SAXS and NMR, FT-IR, THz, and fluorescence spectroscopy as well as microscopic techniques, to high pressure perturbation. Indispensable for a state-of-the-art molecular-level understanding are tight links between experiment and simulation. The computational spectrum includes not only ab initio, QM/MM and force field molecular dynamics, but also modern liquid-state statistical mechanics in conjunction with accurate quantum chemistry, to be used to study complementary solvational, dynamical and conformational properties of the systems.