Sprecher
Beschreibung
The effects of ionic liquids (ILs) on proteins are well known and widely studied for various applications [1]. Compared to conventional solvents, ILs exhibit several advantageous properties, as liquid state over a wide temperature range, excellent solvation ability, and high thermal stability. Biocompatible ionic liquids (Bio-Ils) retain these properties while maintaining manageable toxicity levels, making them attractive for pharmaceutical applications [2]. In this work, Hamiltonian Replica Exchange Molecular Dynamics were employed to investigate the effect of concentration changes in choline-derived ionic liquids on the stability and structure of Plasmodium falciparum proteins. The proteins AMA1, MSP1, and MSP2 were studied in aqueous solutions of choline geranate (CAGE), choline lactate (CAL), and choline chloride (CACL) at concentrations of 0.125 M, 0.250 M, 0.5 M, 1.0 M, and 2.0 M. Solvation structures were characterized using Kirkwood–Buff integrals (KBIs) [3] that revealed distinct behaviors among the Bio-ILs. CACL behaves similarly to a conventional salt, showing minimal variation in solvation effects of the concentration and acting as a preferentially excluded, protein-stabilizing cosolvent. In contrast, CAGE and CAL exhibit behavior typical of Bio-ILs: their affinities, as quantified by KBIs, vary with concentration. Although they are not completely excluded from the protein surface, their compensated electrostatic interactions, modulated by the nature of both cations and anions, contribute to protein stabilization. The choline cation also exhibits complex behavior, with variations in accumulation at different distances from the protein surface. Structural analyses based on RMSD and RMSF indicate an optimal concentration range to maintain protein structures in their functional conformations without a very high viscosity. In AMA1, key residues in disordered regions: K489, R503, K508, and R512 were stabilized. The spatial distributions of relevant functional groups of each cosolvent were further characterized using Minimum Distance Distribution Functions and KBIs. These approaches enabled a molecular-level understanding of protein–cosolvent interactions and their impact on protein stability.