Coordination Funds

压力通过比体积的变化作用于生物分子系统的结构和动力学，这主要是由于水合作用或堆积效率的变化。因此，高静水压非常适合于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。压力也是描述自发波动的理想方法，因为波动涉及到体积的变化，而通常在实验中不易获得的高能构象可以通过压力稳定下来。此外，可以改变氢键、静电和疏水相互作用之间的平衡。在这一倡议中，我们希望集中在基于分子水平的自下而上描述压力对生物分子溶液的影响，并使用压力调制来揭示关于基本生物分子过程和反应的重要机制信息。基于对高压条件下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节绘制蛋白质的构象和功能亚态以及分子间相互作用的图谱。压力也将被用来揭示蛋白质组装和分解的信息，并调节膜辅助过程以及酶转化。最后，我们将获得有关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。这些研究将结合一些敏感和强大的生物物理技术，包括SAXS和核磁共振、FT-IR、THz和荧光光谱以及显微技术，以应对高压扰动。对于最先进的分子水平的理解来说，实验和模拟之间的紧密联系是必不可少的。计算谱不仅包括从头算、QM/MM和力场分子动力学，还包括现代液态统计力学和精确量子化学，用于研究体系的互补溶剂性、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.