Variable Regions of Antibodies and T-Cell Receptors May Not Be Sufficient in Molecular Simulations Investigating Binding.

Antibodies and T-cell receptors are important proteins of the immune system that share similar structures. Both contain variable and constant regions. Insight into the dynamics of their binding can be provided by computational simulations. For these simulations the constant regions are often removed to save runtime as binding occurs in the variable regions. Here we present the first study to investigate the effect of removing the constant regions from antibodies and T-cell receptors on such simulations. We performed simulations of an antibody/antigen and T-cell receptor/MHC system with and without constant regions using 10 replicas of 100 ns of each of the four setups. We found that simulations without constant regions show significantly different behavior compared to simulations with constant regions. If the constant regions are not included in the simulations alterations in the binding interface hydrogen bonds and even partial unbinding can occur. These results indicate that constant regions should be included in antibody and T-cell receptor simulations for reliable conclusions to be drawn.