J. Raul Grigera

Interaction of water with α,α-trehalose in solution: molecular dynamics simulation approach

Molecular simulations of an aqueous solution of α,α-trehalose (α-D-glucopyranosylα-D-glucopyranoside) have been carried out to further the understanding of the effect of α,α-trehalose as a protecting agent against water stress in biological systems. The hydrogen-bond network and water dynamics were found to be only slightly altered compared with pure water (SPC/E model). Some internal hydrogen bonds in trehalose stabilize the conformation that was found to have glycosysidic dihedral angles of 215° and 216°. It is found that trehalose can fit into a water structure involving at least ten water molecules per trehalose. Results support the view that the ability of trehalose to protect against water stress is due to the stabilization of biological structures and not to modification of the properties of water.

Collagen stability, hydration and native state

Molecular dynamics simulations of a collagen-like peptide (Pro-Hyp-Gly)4-Pro-Hyp-Ala-(Pro-Hyp-Gly)5 have been done in order to study the contribution of the hydration structure on keeping the native structure of collagen. The simulation shows that the absence of water produces a distortion on the molecular conformation and an increase in the number of intra-molecular hydrogen bonds. This is in agreement with previous experimental results showing the stiffness of collagen under severe drying and its increase in the thermal stability. This dehydrated material does not keep, however, the native structure.

The effect of stereochemistry upon carbohydrate hydration. A molecular dynamics simulation of β-d-galactopyranose and (α,β)-d-talopyranose

Abstract This paper reports a molecular dynamics simulation study of β- d -galactopyranose and (α,β)- d -talopyranose in aqueous solution. Special emphasis was placed on the intramolecular next-nearest neighbour oxygen distances in the carbohydrate molecule and the hydrogen bonding of the hydroxy functionalities of the carbohydrates with water. The average number of hydrogen bonds of the hydroxy groups of the carbohydrates depends on the stereochemistry of the molecule. In contrast to the HO-2 and HO-4 of d - galactopyranose, those of d -talopyranose are shielded. This is a consequence of an intramolecular hydrogen bond between the HO-2 and HO-4 in d -talopyranose, which also explains why the apparent hydrophobicity of d -talose is found to be greater than that of d -galactose.

The Behavior of the Hydrophobic Effect under Pressure and Protein Denaturation

It is well known that proteins denature under high pressure. The mechanism that underlies such a process is still not clearly understood, however, giving way to controversial interpretations. Using molecular dynamics simulation on systems that may be regarded experimentally as limiting examples of the effect of high pressure on globular proteins, such as lysozyme and apomyoglobin, we have effectively reproduced such similarities and differences in behavior as are interpreted from experiment. From the analysis of such data, we explain the experimental evidence at hand through the effect of pressure on the change of water structure, and hence the weakening of the hydrophobic effect that is known to be the main driving force in protein folding.

Hydration of glucose in the rubbery and glassy states studied by molecular dynamics simulation

We have studied the hydration properties of an 85% (w/w) aqueous solution of glucose using molecular dynamics. The experimental values of the relative populations of α and β anomers were introduced into the description of the system. We computed the radial distribution function, hydrogen bond residence times, hydration number and mean lifetimes, as well the mean glucose and water cluster sizes. The simulated glass transition temperature (Tg) of the solution was computed to evaluate the quality of the model; the computed value of 241 K was in fair agreement with the experimental value of 232 K. It was concluded that most of the water molecules are connected to more than one glucose molecule by hydrogen bonds. The residence time of the water molecules in hydration sites changes from one site to another, but for the anomeric and chain-oxygen atoms, the residence time is greater than for the rest. The average residence time goes from 2.00 ps for the rubbery state at 280 K to 5.75 ps for the glassy state at 200 K. The mean value of the cluster size of glucose is very close to the corresponding to full connectivity and does not vary much from the rubbery to the glassy state.

The Role of Hydration on the Mechanism of Allosteric Regulation: In Situ Measurements of the Oxygen-Linked Kinetics of Water Binding to Hemoglobin

We report here the first direct measurements of changes in protein hydration triggered by a functional binding. This task is achieved by weighing hemoglobin (Hb) and myoglobin films exposed to an atmosphere of 98% relative humidity during oxygenation. The binding of the first oxygen molecules to Hb tetramer triggers a change in protein conformation, which increases binding affinity to the remaining empty sites giving rise to the appearance of cooperative phenomena. Although crystallographic data have evidenced that this structural change increases the protein water-accessible surface area, isobaric osmotic stress experiments in aqueous cosolutions have shown that water binding is linked to Hb oxygenation. Now we show that the differential hydration between fully oxygenated and fully deoxygenated states of these proteins, determined by weighing protein films with a quartz crystal microbalance, agree with the ones determined by osmotic stress in aqueous cosolutions, from the linkage between protein oxygen affinity and water activity. The agreements prove that the changes in water activity brought about by adding osmolytes to the buffer solution shift biochemical equilibrium in proportion to the number of water molecules associated with the reaction. The concomitant kinetics of oxygen and of water binding to Hb have been also determined. The data show that the binding of water molecules to the extra protein surface exposed on the transition from the low-affinity T to the high-affinity R conformations of hemoglobin is the rate-limiting step of Hb cooperative reaction. This evidences that water binding is a crucial step on the allosteric mechanism regulating cooperative interactions, and suggests the possibility that environmental water activity might be engaged in the kinetic control of some important reactions in vivo.

An effective pair potential for heavy water

The properties of heavy water are of interest in different disciplines. The simulation of such a substance, particularly in comparison with ordinary water, requires an appropriate interaction potential that allows the simulations of large systems. The potential presented in this work is an efective three-point charge potential type based on the well-known simple point charges/extended model and is named simple point charges/heavy water (SPC/HW). Molecular dynamics simulation done with the SPC/HW potential shows a good agreement with the experimental values for several properties.

GLASS TRANSITION IN AQUEOUS SOLUTIONS OF GLUCOSE. MOLECULAR DYNAMICS SIMULATION

Abstract We have simulated by molecular dynamics the melting and glass transition of aqueous solution of glucose in a wide concentration range. The simulated glass transition temperature ( T g ) are in good agreement with experimental values but the obtained melting temperatures of relatively diluted solutions are below the experimental ones. The ‘glass’ branch of the temperature-concentration state diagram is quite acceptable and opens the possibility of reliable simulation of vitrification processes in carbohydrate solutions.

Classical molecular-dynamics simulation of the hydroxyl radical in water

We have studied the hydration and diffusion of the hydroxyl radical OH0 in water using classical molecular dynamics. We report the atomic radial distribution functions, hydrogen-bond distributions, angular distribution functions, and lifetimes of the hydration structures. The most frequent hydration structure in the OH0 has one water molecule bound to the OH0 oxygen (57% of the time), and one water molecule bound to the OH0 hydrogen (88% of the time). In the hydrogen bonds between the OH0 and the water that surrounds it the OH0 acts mainly as proton donor. These hydrogen bonds take place in a low percentage, indicating little adaptability of the molecule to the structure of the solvent. All hydration structures of the OH0 have shorter lifetimes than those corresponding to the hydration structures of the water molecule. The value of the diffusion coefficient of the OH0 obtained from the simulation was 7.1x10(-9) m2 s(-1), which is higher than those of the water and the OH-.

A MULTICOPY MODELING OF THE WATER DISTRIBUTION IN MACROMOLECULAR CRYSTALS

A multicopy protocol is proposed for modeling macromolecular hydration using diffraction experimental data (X‐ray or neutron) to search for a better description of delocalized water sites than that given by point water models. The model consists of one macromolecule and several copies of each water molecule, refined simultaneously against diffraction data using molecular dynamics techniques. The protocol was applied to BPTI and an RNA tetradecamer. The sites defined by the different copies range from very ordered ones to continuous channels; they fit the density maps and agree with the diffraction amplitudes with an accuracy comparable with usual crystallographic methods. The delocalization of water in channels agrees with the high mobility observed in NMR experiments. Proteins 28:303–312, 1997