Berlin 2024 – scientific programme

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CPP: Fachverband Chemische Physik und Polymerphysik

CPP 15: Poster I

CPP 15.22: Poster

Monday, March 18, 2024, 18:00–20:00, Poster C

Concentration dependent pKa-values in mixtures of trimethylamine N-oxide (TMAO) and amino acids — Julia Keil, •Varun Mandalaparthy, and Nico van der Vegt — Department of Chemistry, Technical University, Darmstadt

The stabilizing effect of trimethylamine N-oxide (TMAO) on proteins is known to be pH-dependent. In our investigation of this pH-dependent action, we studied protonation-deprotonation equilibria in mixed systems containing amino acids and TMAO by performing constant pH molecular dynamics simulations at different pH values. We found that the presence of TMAO causes a decrease in the pKa of acidic and basic groups, while the presence of acidic groups increases the pKa of TMAO. The observed changes in acidity and basicity of the titratable groups correlate with the TMAO concentration. Our results thus indicate a coupling between the equilibria of different titratable groups.

We propose a Wyman-Tanford binding model to explain the underlying mechanism of the observed behavior. Based on this, the accumulation of molecules around a titratable group favors the protonation state which is better stabilized by the presence of these molecules. That leads to a shift in the protonation-deprotonation equilibrium of titratable groups and results in a change of the pKa. More concisely, we find a favorable interaction between deprotonated acidic groups and protonated basic groups and an unfavorable interaction between different protonated basic groups to explain the observed changes of pKa values in mixed solutions of titratable groups.

Keywords: constant pH molecular dynamics simulations; osmolytes; trimethylamine N-oxide (TMAO); acid-base equilibria; coupled chemical reactions