Understanding the structural dynamics of TCR-pMHC complex interactions.
Kass I, Buckle AM, Borg NA.
Trends Immunol. 2014 Nov 11;35(12):604-612. doi: 10.1016/j.it.2014.10.005. [Epub ahead of print]
Exponential growth in simulation complexity over time. Growth is driven by the doubling of computer power every 24 months coupled with algorithmic advances. The complexity of the simulation is represented by the product of the timescale and system size, on the y-axis. Filled circles represent published molecular dynamics (MD) studies.
Dynamics plays an important but underappreciated role in the interaction between the T cell receptor (TCR) and peptide-bound major histocompatibility complex (pMHC). Crystallographic studies have provided key molecular insights into this interaction; however, due to inherent features of the structural approach, the image of TCR-pMHC interactions that has emerged is a static one. In this review, we discuss how molecular dynamics (MD) simulations can complement and extend current experimental methods aimed at examining TCR-pMHC dynamics. We review the insights obtained from studies that leverage MD approaches, and propose that an integrative strategy that harnesses both MD simulations and structural and biophysical methods will provide new inroads into understanding the transitory and dynamic molecular events that dictate TCR signaling and T cell activation.