Relative Movements of Domains in Large Molecules of the Immune System

Abstract

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.

Intramolecular Domain Movements of Free and Bound pMHC and TCR Proteins: A Molecular Dynamics Simulation Study

“…We characterized the relative orientation of the domains TCR V α and TCR V β by the directional cosines between eigenvectors attached to each domain and sampled over time for all trajectories as outlined in the methods section and in our previous paper [29], see Figure 5. The eigenvectors v 1 and w 1 correspond to the main extensions of the respective domain.…”

“…Based on the methods described previously [29] we monitored the relative orientations of intramolecular domains during the time-course of the simulations. For the definition of domains we used the C α atoms of the protein backbone.…”

“…PCA as such yields eigenvectors unique in directions but ambiguous in orientation. To arrive at standardized eigenvectors allowing for comparison between different MD-runs we chose the crystal structure as a reference frame and re-oriented (if necessary) the resulting eigenvectors after performing the PCA [29]. The three orthonormal eigenvectors from the PCA were used to define an eigenvector matrix to serve as a local coordinate system, moving together with the domain, see Figure 2.…”