title: Geometry Dynamics of α -Helices in Different Class I Major Histocompatibility Complexes.
abstract: MHC α-helices form the antigen-binding cleft and are of particular interest for immunological reactions. To monitor these helices in molecular dynamics simulations, we applied a parsimonious fragment-fitting method to trace the axes of the α-helices. Each resulting axis was fitted by polynomials in a least-squares sense and the curvature integral was computed. To find the appropriate polynomial degree, the method was tested on two artificially modelled helices, one performing a bending movement and another a hinge movement. We found that second-order polynomials retrieve predefined parameters of helical motion with minimal relative error. From MD simulations we selected those parts of α-helices that were stable and also close to the TCR/MHC interface. We monitored the curvature integral, generated a ruled surface between the two MHC α-helices, and computed interhelical area and surface torsion, as they changed over time. We found that MHC α-helices undergo rapid but small changes in conformation. The curvature integral of helices proved to be a sensitive measure, which was closely related to changes in shape over time as confirmed by RMSD analysis. We speculate that small changes in the conformation of individual MHC α-helices are part of the intrinsic dynamics induced by engagement with the TCR.
authors.affiliation: Section of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS), Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.
authors.forename: Reiner
authors.initials: R
authors.lastname: Ribarics
authors.affiliation: Section of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS), Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Kenn
authors.affiliation: Section of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS), Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Karch
authors.affiliation: Institute of Information and Communication Technologies (IICT), Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 25A, 1113 Sofia, Bulgaria.
authors.forename: Nevena
authors.initials: N
authors.lastname: Ilieva
authors.affiliation: Section of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS), Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schreiner
mesh_terms: D001665:Binding Sites; D015796:HLA-B27 Antigen / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D054992:Immunological Synapses / Q000737:chemistry / Q000276:immunology; D016018:Least-Squares Analysis; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology
chemical_list: C090660:HLA-B protein, human; D015796:HLA-B27 Antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell