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Orientation of water molecules in the vicinity of the globular protein SNase is studied. It is shown that two types of characteristic orientations can be distinguished among molecules in direct contact with the protein. Approximately 44% of these molecules are oriented by their OH vector towards the nearest protein atom forming a donor hydrogen bond; 20% of them are directed by their oxygen towards the nearest atom while their protons are directed mainly away from the protein. By forming a network of hydrogen bonds with other water molecules, these molecules initiate orientation correlations in the protein environment within a region of 0.45 nm. More distant water molecules are arranged randomly with respect to the protein. The orientation is described by the angle between vector N directed from the water molecule to the nearest protein atom and characteristic vectors of the water molecule (directions OH, OL, and dipole moment D). A more detailed information about orientations is retrieved from a two-dimensional distribution diagram P(cos(θ), φ) representing direction N in a spherical coordinate system associated with the water molecule. The diagram provides an unambiguous description for the orientation of water molecules and allows a quantitative calculation of the fraction of molecules with a specified orientation.

Molecular mobility in the hydration shell of the SNase globular protein in an aqueous solution with cosolvents (urea and trimethylamine oxide) is studied using all-atom molecular dynamic simulations. Average displacements of the molecules initially located in the successive layers around the protein are calculated over the same short period of time to characterize the diffusion mobility of the molecules depending on the distance to the protein. It is shown that solvent molecules have lower mobility near the protein, and the mobility of more distant molecules increases irregularly and correlates with the positions of the distribution function maxima of these molecules around the protein. After the second maximum of these functions, the mobility reaches its bulky values both for water and the cosolvent.

Aqueous solutions of natural osmolytes (trimethylaminoxide (TMAO), urea, and their mixture) at relatively small (biologically relevant) concentrations are analyzed by the all-atom molecular dynamics simulation. In the recent work (Smolin N. et al. PCCP. 2017. 19. P. 6345) it has been noted that in the protein hydration shell the fraction of TMAO molecules is much smaller than that of urea. The urea addition causes a further decrease in the TMAO fraction in the protein hydration shell. This work shows that in binary solutions urea fraction at urea molecules is always larger than the bulk urea concentration. At the same time, the TMAO fraction near TMAO is the same as in the bulk. In ternary solutions, TMAO and urea behave the same as the binary ones, i.e. they do not noticeably affect each other. This means that the behavior of TMAO and urea molecules in the protein hydration shell is associated with protein rather than their interaction with each other.

There are experimental evidences that in the methanol solution of glycyrrhizic acid (GA) and cholesterol, the cholesterol molecules have two different types of the environment. One corresponds to free molecules and another corresponds to the molecules associated with GA. However, the nature of these associates remains unclear. The all-atom molecular dynamics simulation of GA solutions in methanol is performed. It is shown that, contrary to aqueous solutions, GA in methanol does not form small stable clusters, even in the presence of cholesterol. The arising associates do not have distinct structures and exist for no longer than dozens of nanoseconds. The concentrations of these clusters and their stability constants are estimated. It is necessary to assume the existence of larger-scale associates to explain the experimental data.

In a recent work by Zelikman et al.(J. Struct. Chem., 2015, 56(1)), the molecular dynamics simulation of dimers of glycyrrhizic acid (GA) arising from the spontaneous collision of two GA molecules in water is performed. Several relatively stable dimer structures are found, and when a cholesterol molecule is inserted, associates are observed constituting a GA dimer with a cholesterol molecule “stuck” to it. Here, we simulate the associates consisting of three and four GA molecules and a cholesterol molecule. It appears that the cholesterol molecule, as a rule, also locates at the surface of the GA associate. Therewith, the trimers do not form any clear characteristic structures, as dimers do, and the tetramers can be two stuck dimers.

The molecular dynamics simulation of dimers of glycyrrhizic acid (GA) arising from the spontaneous meeting of two GA molecules in water is performed. Shown that the molecules in the dimer are quite close to each other, there is no place between them where another molecule (including water molecule) could fit. The relatively stable structures of dimers are found, which are characterized by the specific values of angles between the terpene skeletons of GA molecules and sugar ends. Due to thermal motion, the spontaneous transitions between these structures occur. The insertion of a molecule of cholesterol in the solution showed that the associates formed from two GA molecules and one cholesterol molecule are, as a rule, one of stable GA dimers with the attached cholesterol molecule.

The crystal structure of previously unknown ammonium succinate peroxosolvate is studied. It is shown that it represents a rare example of the structure where H2O2 molecule forms two donor hydrogen bonds and does participate in any acceptor hydrogen bonds, despite the presence of substantial quantity of nonperoxide active hydrogen atoms.