(3) Adaptively allocating simulation time according to the inter-replicate uncertainty in ∆G concentrated sampling time where there were sampling issues, which generally meant the bound vanish leg. In a rare case where the sampling issue had a timescale amenable to simulation, this algorithm accelerated equilibration. However, we generally found no evidence that the adaptive time allocation algorithm reduced uncertainty for equivalent computational cost, likely because the timescales of sampling issues could not be matched by our simulations.