Long-Term Molecular Dynamics Simulations Reveal Flexibility Properties of a Free and TCR-Bound pMHC-I System

The interactions between peptide(p)-bound major histocompatibility complexes (MHCs) and T cell receptors (TCRs) play an important role during the immune response. Here, we report on a molecular dynamics (MD) simulation study of free and TCR-bound pMHC-I proteins of the LC13-HLA-B* 44:05-pEEYLQAFTY complex. We performed long-term MD simulations of 4 μs each for both free and bound pMHC-TCR systems, employing 10 independent 400 ns replicas for each state. We observed a reduced dynamic flexibility in the central residues of the peptide and the MHC α1-helix upon TCR ligation, indicating a restricted conformational space in the MHC binding groove. Moreover, our data suggest a minimum of 50 to 100 ns simulation time of individual runs and 5 to 10 independent replicas to permit reliable conclusions for biomolecules of comparable complexity and similar descriptors.