Geometry Dynamics of ? -Helices in Different Class I Major Histocompatibility Complexes.

ABSTRACT: MHC ?-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 ?-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 ?-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 ?-helices, and computed interhelical area and surface torsion, as they changed over time. We found that MHC ?-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 ?-helices are part of the intrinsic dynamics induced by engagement with the TCR.

SUBMITTER: Ribarics R 

PROVIDER: S-EPMC4651647 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature