This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. MHC (major histocompatibility complex) molecules are highly polymorphic molecules which are critical in the self versus non-self discrimination of Immune system. The MHC molecules are comprised of two classes, namely MHC type I (comprised of HLA-A (Human leukocyte antigen), HLA-B and HLA-C molecules) and MHC type II molecules (HLA-DQ, HLA-DR and HLA-DP molecules) which have differing immune system functions. MHC molecules belonging to different families may vary from each other from as few as a couple of amino acids to greater than 30 amino acids. However, the HLA molecules in combination with the peptide presented is highly specific in the recognition of self versus non-self. The structural basis of the same is not well understood and remains a subject of much research. In addition the allelic distribution of these genes underscores the critical role played by the system in protection against microbial invaders of the body. The MHC system also forms the basis for autoimmune diseases whose mechanisms are not well understood. In this study we aim to understand the molecular mechanisms by which HLA micropolymorphisms influence the binding of a viral epitope to the MHC class I (HLA-B*44xx molecules). In addition, configurational information regarding the dynamic structure of the HLA-epitope complex will be analyzed to understand the basis of recognition by the TCR (T-cell receptor) which represents the second half of the antigen-antibody recognition puzzle. The study will use the technique of computational molecular dynamics to understand the role of critical amino acid binding residues in the cleft of HLA-B*44xx molecules. The dynamics of peptide flexibility and plasticity are hypothesized to play a critical role in the immune recognition which is a major focus of this study. We expect the study to provide a major understanding regarding the role of HLA-micropolymorphisms in the recognition and signalling of human immune molecules

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZRG1-BCMB-Q (40))
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Carnegie-Mellon University
Biostatistics & Other Math Sci
Schools of Arts and Sciences
United States
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Yonkunas, Michael; Buddhadev, Maiti; Flores Canales, Jose C et al. (2017) Configurational Preference of the Glutamate Receptor Ligand Binding Domain Dimers. Biophys J 112:2291-2300
Earley, Lauriel F; Powers, John M; Adachi, Kei et al. (2017) Adeno-associated Virus (AAV) Assembly-Activating Protein Is Not an Essential Requirement for Capsid Assembly of AAV Serotypes 4, 5, and 11. J Virol 91:
Subramanian, Sandeep; Chaparala, Srilakshmi; Avali, Viji et al. (2016) A pilot study on the prevalence of DNA palindromes in breast cancer genomes. BMC Med Genomics 9:73
Ramakrishnan, N; Tourdot, Richard W; Radhakrishnan, Ravi (2016) Thermodynamic free energy methods to investigate shape transitions in bilayer membranes. Int J Adv Eng Sci Appl Math 8:88-100
Zhang, Yimeng; Li, Xiong; Samonds, Jason M et al. (2016) Relating functional connectivity in V1 neural circuits and 3D natural scenes using Boltzmann machines. Vision Res 120:121-31
Lee, Wei-Chung Allen; Bonin, Vincent; Reed, Michael et al. (2016) Anatomy and function of an excitatory network in the visual cortex. Nature 532:370-4
Murty, Vishnu P; Calabro, Finnegan; Luna, Beatriz (2016) The role of experience in adolescent cognitive development: Integration of executive, memory, and mesolimbic systems. Neurosci Biobehav Rev 70:46-58
Lee, Tai Sing (2015) The visual system's internal model of the world. Proc IEEE Inst Electr Electron Eng 103:1359-1378
Kuhlman, Chris J; Anil Kumar, V S; Marathe, Madhav V et al. (2015) Inhibiting diffusion of complex contagions in social networks: theoretical and experimental results. Data Min Knowl Discov 29:423-465
Jurkowitz, Marianne S; Patel, Aalapi; Wu, Lai-Chu et al. (2015) The YhhN protein of Legionella pneumophila is a Lysoplasmalogenase. Biochim Biophys Acta 1848:742-51

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