Do we need the constant regions of Antibodies and T-cell receptors in molecular simulations?

At this week’s journal club I presented my latest results on the effect of the constant regions of antibodies (ABs) and T-cell receptors (TCRs) on the dynamics of the overall system. Not including constant regions in such simulations is a commonly used simplification that is found throughout the literature. This is mainly due a massive saving in computational runtime as illustrated below: cutConstRegions

The constant regions contain about 210 residues but an additional speed up comes from the much smaller solvation box. If a cubic solvation box is used then the effect is even more severe:

waterbathBut the question is: “Is is OK to remove the constant regions of an AB or TCR and simulate without them?”.

Using replica simulations we found that simulations with and without constant regions lead to (on average) significantly different results. The detail of our analysis will soon be submitted to a scientific journal. The current working title is “Why constant regions are essential in antibody and T-cell receptor Molecular Dynamics simulations”.