Coordination Funds

压力通过比容的变化作用于生物分子系统的结构和动力学，比容的变化主要是由于水合作用或填充效率的变化。因此，高静水压非常适合研究溶剂化在蛋白质和其他生物分子的折叠、动力学和相互作用中的作用。压力也是表征自发波动的理想方法，因为波动涉及体积的变化，并且通常不容易通过实验获得的高能构象可以通过压力稳定。此外，氢键、静电和疏水相互作用之间的平衡可以改变。在这项倡议中，我们希望专注于基于分子水平的自下而上的描述压力对生物分子溶液的影响，并使用压力调制来揭示基本生物分子过程和反应的重要机制信息。基于在高压条件下对生物小分子和相容溶质的精确参考研究，我们正在通过压力调制绘制蛋白质的构象和功能亚态以及分子间相互作用。压力还将用于揭示蛋白质组装和拆卸的信息，并调节膜辅助过程以及酶促转化。最后，将获得关于蛋白质在极端环境条件下的结构、动力学和功能特性的宝贵信息。这些研究将耦合一些敏感和强大的生物物理技术，包括SAXS和NMR，FT-IR，THz和荧光光谱以及显微镜技术，高压扰动。实验和模拟之间的紧密联系是最先进的分子水平理解的基础。计算谱不仅包括从头算，QM/MM和力场分子动力学，而且现代液态统计力学与精确的量子化学相结合，用于研究系统的互补溶剂化，动力学和构象性质。

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.