Analysis of Key Parameters for Molecular Dynamics of pMHC Molecules

Ulrich Omasits (1) , Bernhard Knapp (2) , Martin Neumann (3) , Othmar Steinhauser (4) , Hannes Stockinger (5) , Rene Kobler (6) , Wolfgang Schreiner (2)

1 Core Unit for Medical Statistics and Informatics
2 Core Unit for Medical Statistics and Informatics
3 Institute of Experimental Physics
4 Department of Computational Biological Chemistry
5 Department of Molecular Immunology
6 Institute of Graphics and Parallel Processing

Molecular dynamics (MD) studies of human major histocompatibility complex (MHC) HLA B*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 pMHC dynamics to T cell activation.

Mots clés: Physical Sciences

Ulrich Omasits, Bernhard Knapp, Martin Neumann, Othmar Steinhauser, Hannes Stockinger, et al.. Analysis of Key Parameters for Molecular Dynamics of pMHC Molecules. Molecular Simulation, 2008, 34 (08), pp.781-793. ⟨10.1080/08927020802256298⟩. ⟨hal-00515047⟩