Simulations of Plasmodium falciparum surface proteins in biocompatible ionic liquids as vaccine adjuvants

Abstract

Vaccine adjuvants are additives that assist in the immune response to antigens. The choice of adjuvants is limited by their effects on antigen stability or their affinity for antibodies, in addition to their potential toxicity and solubility. Recently, a new class of compounds, biocompatible ionic liquids (bio-IL) have been studied as vaccine adjuvants because they have great protein solvation capacity, thermal and chemical stability, and solubility in water or organic solvents. These compounds are an interesting alternative for enhancing the immunological effect of vaccines, and can facilitate the logistics of their transportation and storage.The present project seeks to study the interactions between bio-ILs solutions and proteins on the surface of the Plasmodium falciparum merozoite, the main causative agent of malaria. These proteins are relevant targets for the development of antimalarial vaccines, and bio-ILs can be used as vaccine adjuvants. The study involves molecular dynamics simulations with expanded sampling of antigens in solution. The structure and thermodynamics of solvation will be studied using minimum distance distribution functions and Kirkwood-Buff solvation theory. These methods allow for molecular-scale analysis of the interactions between proteins and complex solvents such as bio-IL, and the effect of these interactions on the stability of individual proteins or protein complexes.This project continues the master's thesis work in which the student studied the interaction mechanism of intrinsically disordered proteins (IDPs) of Plasmodium falciparum through Molecular Dynamics (DM), resulting in a review article and an original article that are submitted for publication.