For example, the ranges between the lower and upper bound for these 2 strategies for each system is ~1 kcal mol -1 for PTP1B, between 1.2-1.9 kcal mol -1 for MtPriA and 2.1-2.2 kcal mol -1 for yTPI, Table . Further and as observed in the probability densities (Figure ), the longer sampling procedures can give rise to erroneous results as seen in yTPI's 10 x 100 procedure (due to loop opening events), and in all 3 systems the increased sampling had no notable improvement on the confidence interval ranges (Table ). On this basis, the longer sampling strategies are likely to be unnecessary as they do not increase precision and of course, require substantially more compute time.