We evaluated a workflow to reliably sample the conformational space of a set of 47 peptidic macrocycles. Starting from SMILES strings, we use accelerated molecular dynamics simulations to overcome high energy barriers, in particular, the cis-trans isomerization of peptide bonds. We find that our approach performs very well in polar solvents like water and dimethyl sulfoxide. Interestingly, the protonation state of a secondary amine in the ring only slightly influences the conformational ensembles of our test systems. For several of the macrocycles, determining the conformational distribution in chloroform turns out to be considerably more challenging. Especially, the choice of partial charges crucially influences the ensembles in chloroform. We address these challenges by modifying initial structures and the choice of partial charges. Our results suggest that special care has to be taken to understand the configurational distribution in apolar solvents, which is a key step toward a reliable prediction of membrane permeation of macrocycles and their chameleonic properties.