From compatible solutes to ribozymes at HHP conditions

HHP 条件下从相容溶质到核酶

• 批准号: 243203486
• 负责人: Professor Dr. Dominik Marx
• 金额: --
• 依托单位: Lehrstuhl für Theoretische Chemie
• 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 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/243203486?language=en
• 关键词: compatible; solutes; ribozymes; HHP; conditions

The key idea underlying this subproject is to use ab initio simulation and its QM/MM extension to predictively explore the dynamical landscape of both small solutes of biomolecular relevance and of functional biomolecules at pressures in the kilobar regime. In the past funding period, we established the machinery, both at the level of simulation and at the level of novel analysis tools, which allows us to quantitatively compute and to assign infrared spectra of small molecular solutes such as TMAO(aq) from the mid-infrared down to the far-IR (THz) frequency range at kilobar pressures. These techniques will now be applied to study systematically more complex solutes such as amino acids and model peptides in an effort to quantitatively understand the pressure-response of hydrophilic and hydrophobic groups in terms of vibrational spectroscopy probes. Based on advances made for TMAO(aq) solutions at high pressures, full ab initio simulations will be an important collaborative contribution toward the rational design of high-pressure force fields for protein simulations. Finally, having obtained first insights into the conformational pressure-response of the reactive site of hairpin ribozyme in the first funding period, the thrust will now shift toward elucidating the pressure-response of the enzymatic step itself, which is the self-cleavage reaction, using QM/MM molecular dynamics simulations.

该子项目的关键思想是使用从头计算模拟及其QM/MM扩展来预测性地探索生物分子相关的小溶质和功能性生物分子在压力下的动力学景观。在过去的资助期间，我们建立了模拟和新型分析工具的机器，这使我们能够定量计算和分配小分子溶质的红外光谱，如TMAO（aq）从中红外到远红外（THz）频率范围，在压力下。这些技术现在将被应用于系统地研究更复杂的溶质，如氨基酸和模型肽，以定量地了解亲水性和疏水性基团的振动光谱探针的压力响应。基于TMAO（aq）在高压下的解决方案所取得的进展，完整的从头算模拟将是对蛋白质模拟高压力场合理设计的重要合作贡献。 最后，在第一个资助期内获得了发夹核酶反应位点的构象压力响应的第一个见解，现在的推力将转向阐明酶促步骤本身的压力响应，这是自切割反应，使用QM/MM分子动力学模拟。