<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Effect of O-glycans on the Structure and Viscosity of Intrinsically Disordered and Glycosylated Protein Lubricin"^^ . "Synovial joints exhibit remarkable lubrication mechanisms, essential for the smooth articulation of bones. \r\nThis intricate process is orchestrated by key biomolecular components, such as hyaluronic acid, lipids, aggrecan, and glycoproteins. \r\nLubricin, characterized by its intrinsically disordered region and highly glycosylated structure, is part of these glycoproteins.\r\nLubricin significantly contributes to reducing viscosity and ensuring the sustained efficacy of synovial joints.\r\nThe protein comprises two globular end domains and an intrinsically disordered central domain.\r\nThe end domains bind to cartilage surfaces, allowing the remaining protein to extend into the synovial fluid. \r\nThe central domain, known as the mucin-like domain, is abundant in O-glycans and mainly responsible for lubricin functionality.\r\nThe O-glycans constitute approximately 30-35\\% of the entire lubricin structure.\r\nO-glycans play a pivotal role in enabling lubricin to fulfill its highly specialized function.\r\nDespite the recognized importance of O-glycans, a detailed understanding of their influence on the structure and viscosity of lubricin remains elusive. \r\n\r\nUsing extensive molecular dynamics (MD) simulations, in this thesis we unveil the influence of O-glycans on the rheological and viscosity properties of lubricin. \r\nIn the first part of this thesis, our focus was on understanding how O-glycans influence the structure of lubricin. \r\nTo achieve this, glycosylated fragments of lubricin were generated and modeled, and a suitable force field for intrinsically disordered glycoproteins was prepared. \r\nFive different segments of lubricin, each with a length of 80 amino acids, were considered. Utilizing Monte Carlo sampling, six different glycosylated fragments were introduced for each segment. \r\nEquilibrium molecular dynamics simulations were then conducted to explore the role of glycans in the conformational properties of lubricin.\r\nThe findings reveal that the presence of O-glycans induces a more extended conformation in fragments of the disordered region of lubricin, resulting in a stiffer structure, and enhancing the exposure of lubricin to solvent molecules.\r\nThese changes in the lubricin structure are attributed to the electrostatic and steric interactions imposed by the bulky side chains of O-glycans.\r\n\r\nThe second phase of our study focused on unraveling the influence of glycans on the viscoelastic behavior of liquid systems containing lubricin fragments. \r\nSpecifically, we aimed to understand how the solution viscosity may have been affected\r\nby the presence of this O-glycosylated protein.\r\nTo achieve this, we employed the Green-Kubo method, i.e. we derived the zero-shear viscosity from the fluctuations\r\nof the pressure tensor in equilibrium molecular dynamics simulations. \r\nIn addition, we carried shear-driven non-equilibrium molecular dynamics simulations to determine the viscosity under\r\nshear.\r\nOur simulations reveal that, unlike pure water, systems containing lubricin display a pronounced shear-thinning response.\r\nFurthermore, our findings demonstrate that glycosylation and the mass density of lubricin chains play a crucial role in regulating the system viscosity and its response to shear. \r\nIncreasing mass density leads to higher viscosity, but the presence of O-glycans results in a reduction in solution viscosity and weakens shear thinning at high shear rates, compared to non-glycosylated systems with the same density.\r\nThe electrostatic and steric interactions of O-glycans prevent the conglomeration and structuring of lubricin fragments, thereby altering the viscoelastic properties of lubricin.\r\n\r\nThe results from our computational study provide a mechanistic understanding of previous experimental observations of lubricin, offering a more rational comprehension of its function in the synovial fluid."^^ . "2024" . . . . . . . "Saber"^^ . "Boushehri"^^ . "Saber Boushehri"^^ . . . . . . "Effect of O-glycans on the Structure and Viscosity of Intrinsically Disordered and Glycosylated Protein Lubricin (PDF)"^^ . . . "final-thesis.pdf"^^ . . . "Effect of O-glycans on the Structure and Viscosity of Intrinsically Disordered and Glycosylated Protein Lubricin (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Effect of O-glycans on the Structure and Viscosity of Intrinsically Disordered and Glycosylated Protein Lubricin (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Effect of O-glycans on the Structure and Viscosity of Intrinsically Disordered and Glycosylated Protein Lubricin (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Effect of O-glycans on the Structure and Viscosity of Intrinsically Disordered and Glycosylated Protein Lubricin (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Effect of O-glycans on the Structure and Viscosity of Intrinsically Disordered and Glycosylated Protein Lubricin (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #34824 \n\nEffect of O-glycans on the Structure and Viscosity of Intrinsically Disordered and Glycosylated Protein Lubricin\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . .