Molecular basis of peptide recognition by the TCR: Affinity differences calculated using large scale computing

Free energy calculations of the wild-type and the variant human T cell lymphotropic virus type 1 Tax peptide presented by the MHC to the TCR have been performed using large scale massively parallel molecular dynamics simulations. The computed free energy difference (−1.86 ± 0.44 kcal/mol) using alchemical mutation-based thermodynamic integration agrees well with experimental data (−2.9 ± 0.2 kcal/mol). Our simulations exploit state-of-the-art hardware and codes whose algorithms have been optimized for supercomputing platforms. This enables us to simulate larger, more realistic biological systems for longer durations without the imposition of artificial constraints