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The change in partial molar volume (PMV) accompanying the xenon-lysozyme binding was investigated for explaining the molecular mechanism of the pressure reversal of general anesthesia. An increase of the PMV from xenon binding to the substrate binding site of lysozyme was found and the binding is suppressed by pressure while the internal binding did not change the PMV, indicating that loose packing between the anesthetics and the action site can cause the pressure reversal of general anesthesia.

The three-dimensional reference site model (3D-RISM) theory is applied to the analysis of hydration effects on the partial molar volume of proteins. The volume differences between low-and high-pressure structures of lysozyme are analyzed by the method.

A new computational method is developed for mapping of small ligand molecules on protein surfaces, which is in line with fragment-drug design, and this method has used three-dimensional reference interaction site model (3D-RISM) theory. The results have shown that some binding modes are affected by the ligand concentration.

CO escaping pathways of Myoglobin are examined in terms of three-dimensional (3D) distribution function that is calculated by the 3D-RISM theory. The partial molar volume changes through the CO escaping pathways have agreed with those from the experiment.

The three-dimensional distribution function theory of molecular liquids is used to study the binding of noble gases to the hen egg-white lysozyme in the aqueous solution. The analysis can also be easily used for predicting the protein-ligand binding sites and affinities.

The molecular mechanism of the effect of ureas and glycerol cosolvents on the partial molar volume (PMV) change associated with the pressure denaturation of staphylococcal nuclease (SNase) protein is described. The PMV of the native SNase in water predicted by 3D-RISM theory is in good accordance with experiment and it is found that the PMV changes associated with pressure denaturation in water and in water-urea and water-glycerol mixtures are qualitatively reproduced.

The partial molar volume and partial molar compressibility of alkali-halide ions in aqueous solution at infinite dilution are calculated. Partial molar volume and compressibility are analyzed by using the hydration shell model, which enables to distinguish a contribution from each hydration shell.

The ion binding by human lysozyme is examined in ionic solutions with the help of the three-dimensional (3D) RISM theory. The results have suggested that the theory could be applied to the selective transmission of ions by a channel protein.

AcrB is a membrane protein and a multidrug efflux transporter. Although the recently solved X-ray crystal structures of AcrB provide a rough sketch of how drugs efflux, the pathway and mechanism have not been completely elucidated. In this study, a ligand-mapping method based on the 3D-RISM molecular theory of solvation, which we recently developed, is applied to AcrB in order to identify the drug efflux pathway. We use a fragment-based approach as a strategy to map chemical functionality on the internal surfaces. A few “multifunctional” ligand-binding sites, which recognize various types of functional groups, are detected inside the porter domain. Spatial links between the multifunctional sites indicate a probable multidrug efflux pathway. The frustrated environment of the protein cavity constructed of weak interactions between ligand and protein may be a mechanism for allowing smooth transportation through the protein. Guided diffusion appears to be the main mechanism for efflux. [ABSTRACT FROM AUTHOR]

This article focuses on a study according to which water molecules in a protein cavity were detected by a statistical-mechanical theory. Water molecules confined inside cavities in a protein are of great importance in understanding the structure, stability, and functions of the biomolecule. The simulation of such water molecules is as difficult as the protein folding itself. The study proves unambiguously that the common understanding was really a prejudice. It is interesting to compare the hydration structure obtained by the 3D-RISM theory with crystallographic water sites of X-ray structure.

Fifteen glycosyl-oxystearates were synthesized by Crich's 4,6-benzylidene and Köening-Knorr strategies. Assessment of structure-activity relationships using macrophage-inducible C-type lectin (Mincle) receptor cells expressing nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) revealed that four dimannopyranosyl-oxystearate analogues were Mincle agonists and that 12- O -(2- O -α-d-mannopyranosyl)-α-d-mannopyranosyl-oxystearate was as an activator of both mouse and human Mincle., Competing Interests: The authors declare no competing financial interest.