Analysis of key parameters for molecular dynamics of pMHC molecules

Molecular dynamics (MD) studies of human major histocompatibility complex (MHC) HLAB*2705 complexing two different peptides were performed. During simulation one peptide partially detached from the MHC while the other peptide switched back and forth between several different configurations. These different configurations relate to conformational substates and can be assigned to different levels of chemical activity or even the molecular mechanisms of immunological signalling. To ensure reliable immunological conclusions from MD simulations we prepare the methodological tools by carefully evaluating initial conditions, system simplification, solvation shell thickness, water model/force field combination and simulation length. We also derive a guideline for appropriate model selection. This kind of quality assessment is seen a mandatory prerequisite for coming studies linking peptide-loaded MHC dynamics to T-cell activation.