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

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.

The impact of the proposed research will be discussed in four main areas: economy, knowledge, people, and society.

Economy

This proposal concerns relatively fundamental physical-chemistry research applied to biological systems with tangible routes to economic impact. The research addresses EPSRC priorities in the life sciences and the EPSRC grand challenge of understanding the physics of life. Solvation of reactants, intermediates, and products is crucial in determining the reaction pathways in industrial chemical processes and biological processes in the living cell. Furthermore, solvation is critical in understanding key societal challenges such as green chemistry, catalysis, and energy storage (batteries and fuel cells). The understanding of biomolecular solvation generated by the work proposed here will have an economic impact in as far as this information feeds back to the relevant groups. Through our strong links with theory collaborators (in particular, Hynes and Laage), we will ensure that fundamental insights will propagate effectively to practitioners in the life sciences.

We have contact with the engineering community through a visiting professorship and the Glasgow-based EPSRC Centre for Innovative Manufacturing (funded by EPSRC, SFC, and industry) will bring us into direct contact with a user group of potential investors and industrialists. Through this and assisted by the University of Glasgow Research & Enterprise, we aim to leverage further funding including direct support from engagement with industry and to explore commercialisation.

Finally, we are keen to share research equipment with the strategic aim to collaborate across traditional scientific boundaries, to develop new research strands, and to explore routes to impact.

Knowledge

The knowledge generated by the proposed work will be communicated through standard routes: papers, conferences, etc. Other channels of knowledge transfer include the organisation of conferences, an area in which the PI has a strong track record. Of particular relevance to this proposal is the organisation by the PI and Mischa Bonn (Director MPI for Polymer Research, Mainz) of a session on Biomolecular Terahertz Spectroscopy part of the BIOS section of the SPIE Photonics West Conference (2013, San Francisco). Further meetings to be organised are a Faraday Discussion meeting (Bristol 2013), regular Ultrafast Chemical Physics (UCP) meetings, and the International Conference on Time-Resolved Vibrational Spectroscopy.

People

The research proposal under consideration here is people centred and career development of the team members a key aim. A critical aspect of this is the ultrafast chemical physics collaboration between the PI and colleagues at the University of Strathclyde. This local collaboration is a centre of excellence in advanced femtosecond spectroscopy and a way to share research equipment. The work proposed here will contribute to the development of career advancing skills amongst the members of the team. The PI has a history of successfully mentoring undergraduate and postgraduate students and postdocs. It is hoped that this good track record can be continued through the appropriate mentoring of PDRAs and PGRSs.

Society

It will be attempted to communicate a flavour of the research enterprise and its results to the public. The PI is the designer of a number of websites, contributes to a blog, while the group has a YouTube channel and a Twitter feed.