M.A. Thesis:

Investigation of Structural Changes in HMGB۱ During Interaction with TLRs by Bioinformatics Tools

The immune response of the body by makes use of soluble factors, ranging from small molecules to large proteins. The best known subset of these soluble factors is cytokines small, inducible proteins that both promote and sequester inflammation. The best known subset of these soluble factors is cytokines, inducible proteins that both promote and sequester inflammation. Pro-inflammatory cytokines are crucial for fighting infection and establishing immunity. Recently, other proteins, such as danger-associated molecular patterns (DAMPs), have also been appreciated for their role in inflammation and immunity. In contrast to cytokines, DAMPs typically bind with a lower affinity and lack dedicated receptors HMGB1 as an example of DAMPs in conjunction with other factors, such as cytokines, chemokines and growth factors,is Coordinator of inflammatory and immune response. HMGB1 binds to a wide range of receptors, most notably TLR4. In many cases, this binding is enhanced or potentiated by binding to a wide variety of other factors, including like lipopolysaccharide and other factors. With the development of computer-based methods, biological research, especially immunology speed and power increased considerably. In this study, molecular dynamics simulation on the structure of HMGB1 for structural changes and behaviour in the cytosol was performed for 40 nanoseconds. Molecular docking simulation to consider how HMGB1 binding to the TLR4 receptor and other factors contribute to creating an inflammatory response were performed. According to the results of the simulation, structural changes of HMGB1 and how to binding it with other factors was determined at the end, drug candidates to inhibit HMGB1 using CADD methods were identified

Keywords: Sterile infection, DAMP, Molecular dynamics Simulation, Molecular Docking Simulation