We note that while the adaptive algorithm produces desirable improvements in the rate of convergence, it was intended to reduce uncertainty. It fails at this for PIP2, at least at earlier total sampling times (Figure ). This is explained by the large bias in initial conformations, in which the chlorophenyl rings are always parallel. Concentrating sampling around the λ = 0.1 region in fact initially increases the inter-run uncertainty, because it results in a wider, but less biased, spread of free energies. If each window were initialised by a conformation which had been thoroughly equilibrated at the given value of λ, this algorithm should instead produce a reduction in uncertainty, as intended.