For telithromycin, all four force fields perform well in water, with a fraction of violations over 0.05 nm of about 0.1. In chloroform, however, all force fields exhibit a fraction of violations of 0.2 or higher. The two most populated clusters are more folded in water (Figure ), whereas they are rather open in chloroform (Figure ). However, there are multiple NOE bound violations in chloroform, indicating that the conformation should also be more folded and exhibit additional intramolecular contacts. In summary, the conformations of both roxithromycin and telithromycin are sensitive to the environment, i.e., chloroform or water, and inaccurate populations of folded and unfolded conformations seem to contribute to the deviations between the computed ensembles and the experimental NOE data.