The Multiple Roles of Waters in Protein Solvation

Abstract

Extensive molecular dynamics (MD) simulations have been used to characterize the multiple roles of water in solvating different types of proteins under different environmental conditions. We analyzed a small set of proteins, representative of the most prevalent meta-folds under native conditions, in the presence of crowding agents, and at high temperature with or without high concentration of urea. We considered also a protein in the unfolded state as characterized by NMR and atomistic MD simulations. Our results outline the main characteristics of the hydration environment of proteins and illustrate the dramatic plasticity of water, and its chameleonic ability to stabilize proteins under a variety of conditions.

An in-depth look at DNA crystals through the prism of molecular dynamics simulations

“…Water molecules and SPM are also affected by the crowded and highly negatively charged environment produced by the packing of the backbone phosphate groups of neighboring duplexes. The rescaled diffusion coefficient 34 of water molecules (Supp. Figure S18 and Supp.…”

“…Diffusion coefficients were calculated from a linear fit of mean square displacements over time using Einstein's equation. The effective temperature of water molecules in crystals was estimated from the corresponding diffusion coefficients which were first scaled by 1/2.56 (to account for the overestimation of the water diffusion by the TIP3P water model) as described in our previous work, 34 while effective DNA temperature was inferred at the base pair step level from the analysis of helical covariance matrices, which provided the stiffness matrices associated to harmonic deformations in the helical space. 35 Essential dynamics was determined by the diagonalization of the Cartesian covariance matrices.…”

Advances in Computational Prediction of Regioselective and Isoform-Specific Drug Metabolism Catalyzed by CYP450s.

“…Protein conformations can be sampled by Monte Carlo methods or with all atom molecular dynamics (MD) simulations. With the emergence of GPU technology, the area of MD simulations has seen great progress over the last 7–10 years . This has also propelled developments and applications of MD in the field of SOM predictions.…”

In Silico Studies of Small Molecule Interactions with Enzymes Reveal Aspects of Catalytic Function

“…Being in close proximity to the protein, it plays an important role in many physiological functions and is crucial to protein folding, protein stability, molecular recognition, ligand binding or release, and catalytic activity [ 13 , 57 – 59 ]. Using the distance of a water molecule from the protein surface, water can be categorized as bulk water, hydration water, and bound water [ 60 – 62 ]. Bulk water molecules maintain a distance longer than the van der Waals radius from the protein surface and facilitate protein diffusion relative to other interacting molecules.…”

“…Clustering techniques were found to be critical in order to overcome the influence of simulation lengths and starting conformations on the prediction of hydration sites and desolvation energies of protein due to the replacement of water molecules upon ligand binding [ 71 , 98 ]. MD simulations have been performed on a set of proteins to investigate how protein solvation is affected by environmental changes, such as an increase in the temperature [ 97 ], and by adding urea or crowding agents [ 62 , 104 ]. Water dynamics within the hydration shell can be analyzed through reorientation dynamics and residence times of water, local tetrahedral order in water, distribution and retardation maps of water around protein, and H-bond strength between water and protein.…”