Dresden 2026 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 4: Computational Biophysics II
BP 4.3: Vortrag
Montag, 9. März 2026, 15:45–16:00, BAR/SCHÖ
Osmolyte Effects on Protein Stability: Charge-Regulation is Essential — •Julia Keil and Nico F. A. van der Vegt — Technische Universität Darmstadt, Germany
Osmolytes such as glycine modulate protein stability through differences in their preferential interactions with folded and unfolded states. In this work, we revisit glycine’s influence on protein stability by explicitly incorporating charge-regulation effects - protonation and deprotonation of titratable groups - into our study of glycine-protein interactions. Using constant-pH molecular dynamics simulations[1], we develop a titratable glycine model. This pH-dependent model predicts that at pH 7 glycine is depleted from nonpolar elastin-like polypeptides (ELPs) but enriched near acidic and basic ELP residues. It also shows a pH-dependent accumulation of glycine around ELPs and the mini-proteins Trp-cage and GB1, both consistent with prior experimental and computational observations[2-4]. Notably, charge regulation produces systematically stronger preferential binding of glycine to ELPs and mini-proteins at neutral pH than predicted by fixed-charge models. Although glycine is zwitterionic in bulk solution at pH 7, acid-base interactions with NH3+ and COO− protein groups alter its protonation state within biomolecular hydration shells. The corresponding shifts in apparent pKa values promote electrostatically favorable combinations of protonation states, providing a mechanistic explanation for the enhanced preferential binding. [1] J. Chem. Theory Comput. 2022, 18, 10,6148-6160 [2] PNAS 2017, 114, 10, 2479-2484 [3] J. Phys. Chem. B 2020, 124, 30, 6565-6574 [4] Biochem. 1987, 26, 16, 5147-5153
Keywords: pKa shifts; acid-base equilibria; molecular dynamics simulations; preferential binding; mini-proteins