BRIEF: This meeting will focus on the role of water in the stability, dynamics and function of biomolecules, rooted in a molecular, microscopic and mechanistic perspective. While the importance of water as a solvent for biomolecular processes has been realized for decades, new experimental and theoretical developments provide revealing, quantitative insights into coupled solute-solvent dynamics and water-mediated interactions on the molecular scale, which go beyond hydrophobic effects. In fact, the very idea of what site or surface displays hydrophobicity is found to be highly context dependent, and requires foundational study, both theoretical and experimental. A diverse group of researchers consisting of experimentalists and theoreticians from around the globe will assemble, whose work has transformed our understanding of water in biomolecular systems as a solvent and structural component of biomolecules and biomolecular complexes. The common goal of this TSRC workshop will be to find convergence in our understanding of this highly exciting topic of biological hydration that, traditionally, has been rife with controversy and disagreements. Our means to find common understanding will be through sharing data and simulation methods, and the comparison of different theoretical, and experimental, approaches on common systems and questions.
WHY NOW: Recent developments that may be game changers for the field include the quantitative description of solvation contributions to the free energy surface on which biomolecular processes take place, including molecular recognition, conformational transitions of proteins, and enzymatically catalyzed reactions. Advances in this area are simultaneously driven by novel computational tools that extract information from simulations, in parallel to cutting-edge experimental tools that interrogate properties of water buried within biomolecules or at biomolecular interfaces and solvent-exposed surfaces. Examples are spatial decompositions of solvation free energy contributions in computer simulations and continuum theories, nuclear magnetic relaxation and Overhauser dynamic nuclear polarization spectroscopy experiments, which are sensitive to the dynamics of water molecules in the vicinity of local probes, linear and non-linear absorption and scattering spectroscopies which report on water hydrogen bond networks, and transient absorption that allows for kinetic insights. These emerging new tools improve our understanding of biomolecular folding/unfolding equilibria and driving forces for complex formation, which in turn will improve our ability to design complex molecular systems with desired functionality in aqueous solution.