Mechanochemistry: pre-stress for tuning biochemical reactions in proteins

机械化学：用于调节蛋白质生化反应的预应力

• 批准号: 83944887
• 负责人: Professorin Dr. Frauke Gräter
• 金额: --
• 依托单位: Interdisziplinäres Zentrum für Wissenschaftliches Rechnen (IWR)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/83944887?language=en
• 关键词: Mechanochemistry; pre; stress; tuning; biochemical

Chemical and enzymatic reactions can be guided by mechanical stress. While single molecule force spectroscopy experiments are an emerging technique to study the chemistry of bond cleavage under external forces, theoretical knowledge to understand or predict the force dependency of reaction rates is limited to simple models. The proposed project aims at examining the effect of force on the electronic and molecular structures and energies during the reaction, including quantum and dynamical effects. We will use combined quantum and molecular mechanical methods, together with enforced transition path sampling, to study and compare two fundamentally different, yet related biologically important reactions, protein disulphide bond reduction by chemical reducing agents and by the protein thioredoxin, and peptide bond hydrolysis in water and by a zinc metalloprotease. Our results will represent the first systematic study of the mechanochemistry of bond cleavage by nucleophilic attack. This will help to explain how nature makes use of mechanical stress to alter enzymatic function, as a new way of mechanotransduction.

化学反应和酶促反应可以由机械应力引导。虽然单分子力谱实验是研究外力作用下键裂解化学的新兴技术，但理解或预测反应速率的力依赖性的理论知识仅限于简单的模型。本项目旨在研究作用力对反应过程中电子和分子结构及能量的影响，包括量子效应和动力学效应。我们将使用量子力学和分子力学相结合的方法，以及强制过渡路径采样，来研究和比较两个根本不同，但相关的生物学重要反应，化学还原剂和蛋白质硫氧还蛋白还原蛋白质二硫化物键，以及锌金属蛋白酶在水中水解肽键。我们的结果将代表第一个系统的机械化学研究的键裂解亲核攻击。这将有助于解释自然如何利用机械应力来改变酶的功能，作为一种新的机械转导方式。

项目成果

Allosteric regulation of focal adhesion kinase by PIP₂ and ATP.

• DOI: 10.1016/j.bpj.2014.11.3454
• 发表时间: 2015-02
• 期刊: Biophysical journal
• 影响因子: 3.4
• 作者: Jing Zhou;A. Bronowska;J. Le Coq;D. Lietha;F. Gräter

Redox potentials of protein disulfide bonds from free-energy calculations.

• DOI: 10.1021/acs.jpcb.5b01051
• 发表时间: 2015-04
• 期刊: The journal of physical chemistry. B
• 作者: Wenjin Li;I. Baldus;F. Gräter