By having access to all isomers of HP-CD, it is natural to discuss which isomers to use when performing simulations. Experimentally, HP-CDs are most often only characterized through the degree of substitution (DS) which is the average number of substituted sidechains in a sample. The DS is determined from mass spectrometry and is obtained from the relative abundances of the observed side-chains. An example is shown in Figure for HP-β-CD where the distribution of isomers ranging from a degree of substitution of 1 to 7 yielding a final degree of substitution of 4.1 is observed. Based on this DS value, the simplest simulation to perform in an effort to replicate any experiment based on the substitutions observed from the HP-β-CD sample presented in Figure would be to use a single structure of HP-CD with degree of substitution of 4 or 5 as they have the highest relative abundance (0.21). However, the HP-CD force field we construct in this work enables the use of representative ensembles of CDs derived from experiments. By selecting a number of simulations to perform in total, N sim , it is possible from mass spectrometry data (Figure ) to generate a distribution of isomers with appropriate degrees of substitution to be used in simulations. In principle such an approach can be scaled to the required computational resources available or until the free energy of binding converges, i.e., including further samples yields no new information.