Dottorato in SCIENZE CHIMICHE

Titolo della tesi: Polarizable Force Field for amino acid based ionic liquids: An extension of AMOEBA force field

The Choline Amino Acid Ionic Liquids (ChAAILs), even with less thermal stability and solvation capacity, granted un high level of biocompatibility compared to the traditional ILs based on imidazolium where a micromolar concentration can lead to half of cellular vitality. The primary goal of the research project was to develop fully functional parameters necessary for accurately simulating Choline-based Ammino Acid Ionic Liquids (ChAAILs) using the polarizable force field AMOEBA. We successfully established a robust methodology for parameterizing these novel ions and applied it to create parameters for the choline cation, as well as nine different amino acids. These amino acids were carefully selected to encompass a wide spectrum of potential functional group properties, including alanine, glycine, valine, serine, lysine, cysteine, histidine, phenylalanine, and aspartate. The effectiveness of the new parameters underwent extensive testing, starting from fundamental properties such as electrostatic potential and binding energy between the ions (which were compared with ab initio data) up to bulk properties like density and x-ray factor structure (against experimental and theoretical data in literature) yielding satisfactory results, leading to the final parameters that have been published and are available to the community. The parameters have been derived having always in mind the main scope of the project: creating an extension of the already existing AMOEBA force field, where compatibility with the already existing FF was crucial. Another important feature to achieve was the transferability of the parameters. After completing all the tests, the parameters were used on the same pure liquid bulk to study the long-range structure of the IL and in particular the aggregation phenomena between anions like aspartate and phenylalanine that show a tendency to create nanostructured liquid. In the end, the work was focused on the use of our parameters in conjunction with AMOEBA-Bio and AMOEBA-pro FF to study the solvation of model biomolecules, in particular a small 12-residue peptide and a short 6-bases DNA sequence. The peptide simulation has exhibited a high structural stability in ILs compared to water; results that are in line with the experimental literature. The DNA double-strand has shown the same behavior but it's much more sensible to the external environment which traces a line between different ILs even with a limited pool of simulations (water, glycine-choline, serine-coline, lysine-choline)