Molecular dynamics simulations of betaine-based deep eutectic solvents with varying iso-alcohols chain lengths

Abstract

Betaine-based (BET) deep eutectic solvents (DESs) made with isoalcohols of varying hydrocarbon chain lengths, namely triethylene glycol (TEG), 1, 2-ethanediol (ETD), 1, 3-propanediol (PPD) and 1, 4-butanediol (BTD) were modelled. Their effects on the formation of aqueous biphasic system (ABS) with 2 M dipotassium phosphate salt solution (K2HPO4) as well as the extraction of common protein molecules, bovine serum albumin (BSA), were studied using molecular dynamics simulation with Gromacs. Qualitative and quantitative data were used to analyse the simulation results, which includes visualised systems in equilibrium, root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration, radial distribution function (RDF) and hydrogen bond analysis. The results and literature research validated the role of inorganic salt solute concentration on the phase forming ability as well as the possibility of protein denaturation. More investigations and experimental works are to be carried out regarding the type of inorganic salt and its concentration for aqueous biphasic systems (ABSs) with alcohol based DESs and salt solution for protein extraction purposes. This is essential to understand the salting-out effect and to isolate the effects of hydrocarbon chain length from other influencing factors. Additionally, inorganic salt concentrations, presence of ether linkage as well as hydrocarbon chain length is shown to play a role in the dynamics between molecules in the system as well as protein conformational changes. Overall, ABS incorporating PPD and BTD with hydrocarbon chain lengths not exceeding C4 demonstrated superior performance in terms of protein conformational stability and interaction, showcasing their efficacy in protein extraction process.