Solvation dynamics and structure around proteins and peptides: collective network motions or weak interactions

几乎所有的生物过程都是在水环境中进行的，水的存在对生命是必不可少的。蛋白质的化学作用依赖于蛋白质支架的波动和灵活性。这种灵活性在很大程度上是由水决定的，而与此同时，已知蛋白质会影响周围水的结构和动力学。最近的一些研究使用了非常不同的技术，得出了这样的结论：一种蛋白质将许多水层（7到10层）紧紧地拥抱在一起，这种拥抱被称为“蛋白质之舞”。一些实验，如Zewail小组的实验，表明水在蛋白质附近的动力学急剧减慢，这表明水已经变成了一个杯子。然而，其他研究，如对较小溶质的飞秒红外泵浦探针研究，已经清楚地表明，在第一溶剂化壳层之外，对水的结构和动力学没有影响。因此，我们处于非常不令人满意的位置，由著名团体进行的最新研究完全不同意生物分子与周围水介质的相互作用。在这里，我们建议可以通过更广泛和更合适的频谱覆盖来解决这一冲突。低频红外和拉曼光谱产生了高度争议的结果，仅对约1 ps的狭窄时间尺度范围内的动力学敏感，不能解决较慢和较快的过程。为了解决这个问题，我们将应用一个非常高动态范围时域版本的拉曼光谱，覆盖光谱范围<125 MHz至~30 THz。这将与覆盖100兆赫到200太赫兹光谱范围的宽带介电光谱相结合。这些互补技术将用于解决与蛋白质、多肽和其他具有生物学意义的分子与周围水的相互作用有关的争议，以及表征生物分子本身的低频模式。低温研究将解决有争议的蛋白质动力学转变，特别是溶剂在其中的作用。最后，我们建议研究蛋白质在经历环境参数引起的三级和四级结构变化时集体模式的变化。该研究项目涉及蛋白质、多肽、其他生物分子和周围水溶液的微观结构动力学。这对于理解活细胞的功能、合成生命的设计以及生命的基本物理学都是至关重要的。这个领域处于物理学、生物学和化学的前沿，是未来合成生物工程的基础。目前对合成生命的研究只有在物理设计原则被首先确立的情况下，才会导致未来工业的发展；这是本提案的主要目的。我们与理论合作者的紧密联系将确保基本见解将有效地传播给这些信息的“用户”。

Virtually all biological processes take place in an aqueous environment and the presence of water is essential to life. Chemistry enabled by proteins relies on the fluctuations and flexibility of the protein scaffold. This flexibility is largely determined by water while at the same time the protein is known to affect the structure and dynamics of the surrounding water. A number of recent studies using very different techniques have come to the conclusion that a protein ties many water layers (7 to 10) to itself in an intimate embrace that has been termed the "protein dance". Some experiments, such as those by the Zewail group, suggest a dramatic slowing down of the dynamics of water near a protein suggesting that this water has become a glass. However, other studies such as femtosecond infrared pump-probe studies on smaller solutes have clearly shown no effect on water structure and dynamics beyond the first solvation shell. Thus, we are in the highly unsatisfactory position where state-of-the-art studies by reputable groups completely disagree on the interaction of biomolecules with the surrounding aqueous medium.Here we propose that this conflict can be resolved through a wider and more appropriate spectral coverage. The low frequency infrared and Raman spectroscopy that yielded the highly controversial results is only sensitive to dynamics in a narrow range of timescales around ~1 ps and cannot resolve slower and faster processes. To remedy this, we will apply a very high dynamic range time-domain version of Raman spectroscopy covering the spectral range <125 MHz to ~30 THz. This will be combined with broadband dielectric spectroscopy covering the spectral range 100 MHz to 200 THz. These complementary techniques will be used to solve the controversies relating to the interaction of proteins, peptides, and other molecules of biological significance with the surrounding water as well as to characterise low-frequency modes in the biomolecules themselves. Low temperature studies will address the controversial protein dynamical transition and particularly the role of the solvent in this. Finally, we propose to study changes in the collective modes of proteins as they undergo changes in tertiary and quaternary structure caused by environmental parameters.The research programme addresses the microscopic structural dynamics of proteins, peptides, other biomolecules, and the surrounding aqueous solvent. This is critical to the understanding of the function of the living cell, to the design of synthetic life, and to the fundamental physics of life. This area is at the cusp of physics, biology, and chemistry and underpins future synthetic-biology engineering. Current research into synthetic life will only lead to the development of future industries if the physical design principles have been laid down first; this is the primary aim of this proposal. Our strong links with theory collaborators will ensure that fundamental insights will propagate effectively to the 'users' of such information.