The Study of Molecules and Processes in Solution: An Overview of Questions, Approaches and Applications

Abstract

Many industrial processes, several natural processes involving non-living matter, and all the processes occurring within living organisms take place in solution. This means that the molecules playing active roles in the processes are present within another medium, called solvent. The solute molecules are surrounded by solvent molecules and interact with them. Understanding the nature and strength of these interactions, and the way in which they modify the properties of the solute molecules, is important for a better understanding of the chemical processes occurring in solution, including possible roles of the solvent in those processes. Computational studies can provide a wealth of information on solute–solvent interactions and their effects. Two major models have been developed to this purpose: a model viewing the solvent as a polarisable continuum surrounding the solute molecule, and a model considering a certain number of explicit solvent molecules around a solute molecule. Each of them has its advantages and challenges, and one selects the model that is more suitable for the type of information desired for the specific system under consideration. These studies are important in many areas of chemistry research, from the investigation of the processes occurring within a living organism to drug design and to the design of environmentally benign solvents meant to replace less benign ones in the chemical industry, as envisaged by the green chemistry principles. The paper presents a quick overview of the modelling approaches and an overview of concrete studies, with reference to selected crucial investigation themes.

Efficient Refinement of Complex Structures of Flexible Histone Peptides Using Post-Docking Molecular Dynamics Protocols

“…It has been long recognized that water molecules play key roles in protein folding, stability, filling cavities, and mediating interactions with ligands [ 39 , 130 ]. Peptide ligands like the histone H3 fragments ( Table 1 ) are highly hydrated, and, therefore, water molecules play a central role [ 32 ] during their binding to the target molecules.…”

“…Peptide ligands like the histone H3 fragments ( Table 1 ) are highly hydrated, and, therefore, water molecules play a central role [ 32 ] during their binding to the target molecules. Water molecules in the interface of the binding partners can form adhesive hydrogen-bonded networks between the partners, stabilizing the protein–ligand complex structure [ 39 , 131 ]. However, accurately assigning all water positions in experimental structures determined by X-ray crystallography is challenging due to its limitations often rooted in the inherent mobility of water [ 132 , 133 ].…”

“…Other experimental methods also often suffer from improper or complete lack of water positions [ 133 , 134 , 135 , 136 ], necessitating the use of theoretical methods. Computational studies commonly use MD simulations with explicit solvent models to investigate the above-mentioned roles of water at the atomic level [ 39 ]. However, providing a complete hydration structure of target–ligand complexes is often challenging for the default hydration algorithms of MD simulation packages due to the restricted access of bulk water to interface regions [ 46 ] resulting in an unwanted presence of void (vacuum) cavities in the interface prior to the MD steps.…”

“…Thirdly, peptides have many hydrophilic regions, and, therefore, they are extensively hydrated which further complicates the docking process [ 28 , 29 , 30 , 31 ]. Notably, the elucidation of the role of hydration and water networks is a general problem in drug design that is not restricted to peptide ligands [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. However, incorporating explicit water molecules in molecular docking is rather challenging [ 41 , 42 , 43 , 44 ].…”