Bio-macromolecules are dynamic ensembles, not static structures. We characterise these ensembles to understand how proteins fold, when they misfold, and how enzymes work.
We characterised temperature-induced misfolding of the prion protein, revealing multiple partially disordered intermediates stabilised by non-native hydrogen bonds (Biochemistry, 2017), the mechanism of human prion unfolding (J. Phys. Chem. B, 2017), and the multiple modes of dimerisation that seed aggregation, captured by replica-exchange molecular dynamics (J. Phys. Chem. B, 2016).
We established the molecular-thermodynamic origin of substrate promiscuity in laccase, pointing toward broad-spectrum degraders of dye effluents for green bioremediation (J. Phys. Chem. Lett., 2023). On the therapeutic side, we elucidated how the antidiabetic drug chlorpropamide noncompetitively inhibits acetylcholinesterase through newly identified allosteric sites (Phys. Chem. Chem. Phys., 2024) and mapped the multiple inhibition pathways of organoselenium compounds (J. Phys. Chem. B, 2021) — relevant to Alzheimer's disease.