Corrigendum: Differential geometric analysis of alterations in MH α-helices

Kenn

Journal of Immunology Research

et al. 2015

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.

Section: Introductionmentioning

confidence: 99%

Geometry Dynamics ofα-Helices in Different Class I Major Histocompatibility Complexes

Kenn

Journal of Immunology Research

et al. 2015

Geometric Analysis of Alloreactive HLAα-Helices

BioMed Research International

Ilieva

et al. 2014

Molecular dynamics (MD) is a valuable tool for the investigation of functional elements in biomolecules, providing information on dynamic properties and processes. Previous work by our group has characterized static geometric properties of the two MHC α-helices comprising the peptide binding region recognized by T cells. We build upon this work and used several spline models to approximate the overall shape of MHC α-helices. We applied this technique to a series of MD simulations of alloreactive MHC molecules that allowed us to capture the dynamics of MHC α-helices' steric configurations. Here, we discuss the variability of spline models underlying the geometric analysis with varying polynomial degrees of the splines.

Relative Movements of Domains in Large Molecules of the Immune System

Schreiner

Journal of Immunology Research

et al. 2015

Molecular dynamics was used to simulate large molecules of the immune system (major histocompatibility complex class I, presented epitope, T-cell receptor, and a CD8 coreceptor.) To characterize the relative orientation and movements of domains local coordinate systems (based on principal component analysis) were generated and directional cosines and Euler angles were computed. As a most interesting result, we found that the presence of the coreceptor seems to influence the dynamics within the protein complex, in particular the relative movements of the two α-helices, Gα 1 and Gα 2.