is the original physical parameter, p λ is the parameter prior width and k λ is the mathematical parameter or optimization variable. The linear mapping between mathematical and physical parameters allows one to simultaneously optimize parameters that have different physical units and may vary across many orders of magnitude. The prior width is a hyperparameter that is user-specified for each parameter type, and controls the size of the variations of parameters of that type over the course of the optimization. For a fixed change in the physical parameter, the change in the mathematical parameter is inversely proportional to the prior width, therefore the prior width is proportional to the inverse square of the penalty function contribution. Due to a greater anticipated deviation in the initial parameters compared to those seen in AMBER-FB15, the prior widths for the bond and angle parameters were both increased by a factor of 5. The prior widths used for FB18 are shown in Table .