Coordination Funds

协调基金

• 批准号: 243255053
• 负责人: Professor Dr. Roland Winter
• 金额: --
• 依托单位: Lehrstuhl für Physikalische Chemie I
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/243255053?language=en
• 关键词: Coordination; Funds

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.

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，这主要是由于水合或堆积效率的变化。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、动力学以及相互作用中的作用。压力也是表征自发波动的理想选择，因为波动涉及体积变化，并且通常不易通过实验获得的高能构象异构体可以通过压力来稳定。此外，氢键、静电和疏水相互作用之间的平衡可以改变。在这一举措中，我们希望重点关注基于分子水平的压力对生物分子溶液的影响的自下而上的描述，以及使用压力调节来揭示基本生物分子过程和反应的重要机制信息。基于高压条件下小生物分子和相容溶质的准确参考研究，我们正在通过压力调节绘制蛋白质的构象和功能亚状态以及分子间相互作用。压力还将用于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，将获得有关极端环境条件下蛋白质的结构、动力学和功能特性的宝贵信息。这些研究将结合许多敏感且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技术，与高压扰动。对于最先进的分子水平理解来说，实验和模拟之间的紧密联系是必不可少的。计算范围不仅包括从头算、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、动力学和构象特性。