FOR 1979:  Exploring the Dynamical Landscape of Biomolecular Systems by Pressure Perturbation

• Subject Area: Chemistry ; Thermal Engineering/Process Engineering
• Term: from 2013 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 227612752

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 biomolecular systems exposed to extreme environmental conditions. These studies will couple a number of sensitive and powerful biophysical techniques, including SAXS, X-ray reflectivity, and NMR, FT-IR, THz, and fluorescence spectroscopy as well as microscopy 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 classical molecular dynamics with pressure-optimized force fields, 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.

• DFG Programme: Research Units

Projects

• Characterization of different conformational states of proteins by highpressure NMR spectroscopy (Applicants Kalbitzer, Hans Robert ;  Kremer, Werner )
• Coordination Funds (Applicant Winter, Roland )
• From compatible solutes to ribozymes at HHP conditions (Applicant Marx, Dominik )
• Influence of osmolytes on densities, solubilities, osmotic pressures and reaction kinetics in high-pressure biological systems (Applicant Sadowski, Gabriele )
• Membrane curvature modulation by membrane fusion promoting domains: HHP as a tool to study membrane fusion (Applicant Winter, Roland )
• Multiscale simulations of osmolyte and high-pressure effects on conformational transitions and molecular associations of biomolecular systems (Applicants Horinek, Dominik ;  Kast, Stefan M. )
• Peptide foldamers - structure and function under the influence of high pressure (Applicant Reiser, Oliver )
• Structural determination of biologically relevant systems in the bulk and at interfaces by high pressure X-ray methods (Applicant Nase, Julia )
• THz spectroscopy of compatible solutes at HHP conditions probing changes in the hydration water network (Applicant Havenith-Newen, Martina )
• Unraveling the pressure sensitivity of cytoskeletal microtubules (Applicant Winter, Roland )
• Volume profile of biochemically responsive interfaces (Applicant Czeslik, Claus )

• Spokesperson: Professor Dr. Roland Winter