NCMC moves are implemented in BLUES by first cycling off the interactions between the target and surrounding atoms prior to the move. The electrostatic and then steric interactions are turned off and on by scaling λ (a variable controlling the strength of interactions between the sidechain and the rest of the system) over a given number of n NCMC steps. First, the interactions are scaled from 1 to 0 over a series of n 2 steps, where λ=1 corresponds to full interactions and λ=0 corresponds to no interactions. When all interactions are turned off (at n 2 ), the target atoms are re-positioned -in this case, a sidechain is rotated -and the interactions are scaled back on in reverse order (steric and then electrostatic) from λ=0 to λ=1 over n 2 steps. The total work of decoupling, repositioning and recoupling of the atoms is summed and used to accept or reject the move. NCMC moves are alternated with intervals of traditional molecular dynamics to allow the system to undergo normal dynamics and relax further before attempting additional moves. The number of intermediate MD steps is also be specified by the user. BLUES also provides options for adding extra NCMC steps immediately preceding and following the rotational move (via an option called nprop) as well as freezing atoms distant from the region being perturbed during the NCMC simulation to help limit unintended motion and reduce variance in the work distribution, thereby improving move acceptance. 15, More robust documentation and details as well as the full BLUES package are freely available on GitHub at blues, and detailed in the work of Gill et al.