Institute of Chemistry and Center for Computing in Engineering and Science – State University of Campinas, Campinas, SP, Brazil.
Have you ever heard of ionic liquids? Do you know what they are and what they are used for? Every kitchen has a jar containing salt, which consists mainly of sodium chloride. Salt is a white, solid compound that is very soluble in water. Chemically it is an ionic compound, and usually these compounds are solid. Ionic liquids are interesting precisely because they are liquids at room temperature and, because of this, have unique characteristics that are of interest to the pharmaceutical and chemical industries.
Simulation of a protein in water and ionic liquids
Ionic liquids were discovered in 1951, and have been the subject of many scientific studies ever since. Computational simulations play a central role in the understanding of these compounds, because with them it is possible to study the structures of liquids and interactions with various solutes in molecular detail. In particular, computational studies have been done to understand how Ionic Liquids interact with proteins, promoting their stabilization or denaturation. Each ionic liquid exhibits a distinct behavior depending on its chemical nature and concentration. In general, when an ionic liquid stabilizes a protein, this is because its interactions with the protein surface are unfavorable, stabilizing more compact structures. However, the interactions are quite diverse and complex at the molecular level, and simplified descriptions are usually unsatisfactory.
With this in mind, the group of Professor Leandro Martínez, a researcher at the Institute of Chemistry, University of Campinas (UNICAMP), has been developing a project that aims to describe the solvation structure of proteins by ionic liquids. The study is being conducted through molecular dynamics simulations, which are performed using the computational power of CCES (Center for Computing in Engineering & Sciences). The simulations allow trajectories to be obtained that contain the position of all the atoms, protein, water, and ionic liquid, over time. From these trajectories the distribution of the components of each system around the protein can be calculated.
The distribution of the ionic liquids and water around the protein is obtained by calculating the smallest distance between atoms of the solvents and the protein. It thus differs from the commonly used radial distribution functions and can be applied for solutes of various shapes and complexities. The use of minimum distances makes possible a detailed molecular description of the distribution of the molecules making up the solution around the protein without influence of the shape of the solute.
The study has shown interesting results. It has been observed that the smaller the amount of ionic liquid, the more it is concentrated on the surface of the protein. This indicates that there is a direct interaction of the ionic liquid with the protein, which can result in denaturation of the protein, meaning that the protein can lose its physical and chemical properties. However, as the amount of ionic liquid increases, its interaction with the protein surface becomes unfavorable, and water is concentrated around the protein structure. This scenario where water is the compound that interacts most favorably with the protein surface leads to a preservation of the native structure. At the end of the study, insight is gained into the solvation structure of the proteins in these solutions.
Ionic liquids present great potential in their use as solvents for various substances, catalysts in chemical processes and even as vehicles for drug application. Understanding how they behave in different chemical environments is important to apply them more effectively. Computational tools play a remarkable role in the study of complex systems and, for ionic liquids in particular, theoretical studies are a way to understand how these compounds organize themselves around complex solutes, such as proteins, being indispensable for a deeper understanding of the molecular interactions of these systems.
PICCOLI, V; MARTÍNEZ, L. Estudo da solvatação de proteínas por líquidos iônicos usando funções de distribuição de mínima distância. Escola de Modelagem Molecular de Sistemas Biológicos, 2018, Petrópolis.
MARTÍNEZ, L.; SHIMIZU, S. Molecular Interpretation of Preferential Interactions in Protein Solvation: A Solvent-Shell Perspective by Means of Minimum-Distance Distribution Functions. Journal of chemical theory and computation v. 13, n. 12, p. 6358–6372 , 12 dez. 2017.