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

Abstract EN

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.