Glucose plays a crucial role in the mammalian cell metabolism. In the erythrocytes and endothelial cells of the blood-brain barrier, glucose uptake is mediated by the glucose transporter type 1 (GluT1). GluT1 deficiency or mutations cause severe physiological disorders. GluT1 is also an important target in cancer therapy as it is overexpressed in tumor cells. Previous studies have suggested that GluT1 mediates solute transfer through a cycle of conformational changes. However, the corresponding 3D structures adopted by the transporter during the transfer process remain elusive. In the present work, we first elucidate the whole conformational landscape of GluT1 in the absence of glucose, using long molecular dynamics simulations and show that the transitions can be accomplished through thermal fluctuations. Importantly, we highlight a strong coupling between intracellular and extracellular domains of the protein that contributes to the transmembrane helices reorientation during the transition. The conformations adopted during the simulations differ from the known 3D bacterial homologs structures resolved in similar states. In holo state simulations, we find that glucose transits along the pathway through significant rotational motions, while maintaining hydrogen bonds with the protein. These persistent motions affect side chains orientation, which impacts protein mechanics and allows glucose progression.

One of the main characteristics of blood coagulation is the speed of clot growth. In the current work we consider a mathematical model of the coagulation cascade and study existence, stability and speed of propagation of the reaction-diffusion waves of blood coagulation. We also develop a simplified one-equation model that reflects the main features of the thrombin wave propagation. For this equation we estimate the wave speed analytically. The resulting formulas provide a good approximation for the speed of wave propagation in a more complex model as well as for the experimental data.

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Phycobilisome (PBS) is a giant water-soluble photosynthetic antenna transferring the energy of absorbed light mainly to the photosystem II (PSII) in cyanobacteria. Under the low light conditions, PBSs and PSII dimers form coupled rows where each PBS is attached to the cytoplasmic surface of PSII dimer, and PBSs come into contact with their face surfaces (state 1). The model structure of the PBS core that we have developed earlier by comparison and combination of different fine allophycocyanin crystals, as reported in Zlenko et al. (Photosynth Res 130(1):347-356, 2016b), provides a natural way of the PBS core face-to-face stacking. According to our model, the structure of the protein-protein contact between the neighboring PBS cores in the rows is the same as the contact between the APC hexamers inside the PBS core. As a result, the rates of energy transfer between the cores can occur, and the row of PBS cores acts as an integral PBS "supercore" providing energy transfer between the individual PBS cores. The PBS cores row pitch in our elaborated model (12.4 nm) is very close to the PSII dimers row pitch obtained by the electron microscopy (12.2 nm) that allowed to unite a model of the PBS cores row with a model of the PSII dimers row. Analyzing the resulting model, we have determined the most probable locations of ApcD and ApcE terminal emitter subunits inside the bottom PBS core cylinders and also revealed the chlorophyll molecules of PSII gathering energy from the PBS.

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Vessel occlusion is a perturbation of blood flow inside a blood vessel because of the fibrin clot formation. As a result, blood circulation in the vessel can be slowed down or even stopped. This can provoke the risk of cardiovascular events. In order to explore this phenomenon, we used a previously developed mathematical model of blood clotting to describe the concentrations of blood factors with a reaction-diffusion system of equations. The Navier-Stokes equations were used to model blood flow, and we treated the clot as a porous medium. We identify the conditions of partial or complete occlusion in a small vessel depending on various physical and physiological parameters. In particular, we were interested in the conditions on blood flow and diameter of the wounded area. The existence of a critical flow velocity separating the regimes of partial and complete occlusion was demonstrated through the mathematical investigation of a simplified model of thrombin wave propagation in Poiseuille flow. We observed different regimes of vessel occlusion depending on the model parameters both for the numerical simulations and in the theoretical study. Then, we compared the rate of clot growth in flow obtained in the simulations with experimental data. Both of them showed the existence of different regimes of clot growth depending on the velocity of blood flow.

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The O-antigen is the most variable and highly immunogenic part of the lipopolysaccharide molecule that covers the surface of Gram-negative bacteria and makes up the first line of cellular defense. To provide insight into the details of the O-antigen arrangement on the membrane surface, we simulated its behavior in solution by molecular dynamics. We developed the energetically favorable O-antigen conformation by analyzing free-energy distributions for its disaccharide fragments. Starting from this conformation, we simulated the behavior of the O-antigen chain on long timescales. Depending on the force field and temperature, the single molecule can undergo reversible or irreversible coil-to-globule transitions. The mechanism of these transitions is related either to the rotation of the carbohydrate residues around O-glycosidic bonds or to flips of the pyranose rings. We found that the presence of rhamnose in the O-antigen chain crucially increases its conformational mobility.