Enthalpic and Entropic Contributions to Hydrophobicity

Abstract

Hydrophobic hydration plays a key role in a vast variety of biological processes, ranging from the formation of cells to protein folding and ligand binding. Hydrophobicity scales simplify the complex process of hydration by assigning a value describing the averaged hydrophobic character to each amino acid. Previously published scales were not able to calculate the enthalpic and entropic contributions to the hydrophobicity directly. We present a new method, based on Molecular Dynamics simulations and Grid Inhomogeneous Solvation Theory, that calculates hydrophobicity from enthalpic and entropic contributions. Instead of deriving these quantities from the temperature dependence of the free energy of hydration or as residual of the free energy and the enthalpy, we directly obtain these values from the phase space occupied by water molecules. Additionally, our method is able to identify regions with specific enthalpic and entropic properties, allowing to identify so-called “unhappy water” molecules, which are characterized by weak enthalpic interactions and unfavorable entropic constraints.

Perspectives on the Future of Ice Nucleation Research: Research Needs and Unanswered Questions Identified from Two International Workshops

“…Computer simulations could represent an invaluable tool towards this objective. On the one side, full atomistic simulations could provide a detailed description of the kinetics and thermodynamics of specific proteins at conditions similar to the one of highly controlled experiments [73]. On the other side, coarse-grained models could be used to answer questions related to the common features shared by the various proteins [74][75][76][77].…”

Target SARS-CoV-2: Computation of Binding energies with drugs of Dexamethasone/Umifenovir by Molecular Dynamics using OPLS-AA force field

“…The supremacy of non-bonded interactions stabilize the three-dimensional structure of protein-ligand complex and consists of electrostatic, π-effects, van der Waals forces, H-bonds, hydrophobic effects. In these circumstances, we restrict to the non-bonded interactions [38][39][40][41] between SARS-CoV-2+Dexamethasone/Umifenovir only. Certain non-bonded interactions between the protein and drugs are shown (at 10ns) in figures 1 & 2 [42,43].…”

Molecular design opportunities presented by solvent‐exposed regions of target proteins

“…Consequently, new computational methodologies are needed to predict the position and thermodynamic properties of water molecules (ie, hydration sites) in the binding pocket . At present, it is possible to identify areas of unfavorable bound waters based on molecular dynamics simulations and Grid Inhomogeneous Solvation Theory, which can be used improve the ligand binding by replacing so‐called unhappy waters …”