From compatible solutes to ribozymes at HHP conditions

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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.