On the Thermodynamic Solvation of Biomolecules in Solution

Abstract: The topic solvation thermodynamics is an important aspect of chemistry, dealing with the effects introduced by solvents onto solutes. In particular, biological systems are highly heterogeneous in their choice of solvent typically characterized by either being in a polar or non-polar environment. For example, the cytoplasm of cells constituting the internal environment of cells is an aqueous solvent, whereas the membrane, being the boundary separating the cells from its surroundings, is an example of a lipid solvent. In addition to the main solvent, the majority of biological solvents also contain co-solvents such as ions, including ATP which can be found to be on the ~10 mM cellular concentration scale, or monovalent ions such as potassium, sodium, chloride, and not to forget free amino acids. While the previously mentioned examples are important in their own regards for oxidative phosphorylation, nerve cell communication, and construction of proteins respectively, to mention a few examples, their role as co-solvents can also greatly affect the stability and solubility of molecular matter.In this work, we will investigate the properties underlying the solvation of molecular matter utilizing statistical thermodynamics and molecular simulations. In specific by using molecular simulations we can determine atomistic properties for systems of interest, and via statistical thermodynamics relate these properties to experimental observables. These observables may either be mechanical properties addressing the behavior of molecular matter at a given state, or they may be state functions that describe the changes in energetics and entropy for the molecular matter changing. Within solvation thermodynamics, one of the most important state functions is the chemical potential and highly related solvation free energy describing the free energy of adding a solute particle to the system and thus quantifies the reversible work between the solute and solvent upon introducing the particle, and thus multiple methods are discussed how to obtain this quantity.The findings of the presented research include among others reflections upon the solubility of salt bridges in proteins, and counter-intuitive cation-cation enthalpic attraction due to changes in ion solvations induced via a host molecule. Furthermore, the research also addresses the regulation of co-solvent-induced aggregation. Last, but not least, the total thermodynamic decomposition of caffeine solvation in electrolyte solutions, utilizing energy-representation theory of solvation to unveil the mechanism of anion-specific processes, and demonstrating the capabilities of the method to unlock solvation properties to optimize and rationally design future systems.