Molecular dynamics simulation is a powerful tool for characterizing the solution structural ensembles of cyclic peptides. However, the ability of simulation to recapitulate experimental results and make accurate predictions largely depends on the force fields used. In our work here, we evaluate the performance of seven state-of-the-art force fields in recapitulating the experimental NMR results in water of 12 benchmark cyclic peptides, consisting of 6 cyclic pentapeptides, 4 cyclic hexapeptides, and 2 cyclic heptapeptides. The results show that RSFF2+TIP3P, RSFF2C+TIP3P, and Amber14SB+TIP3P exhibit similar and the best performance, all recapitulating the NMR-derived structure information on 10 cyclic peptides. Amber19SB+OPC successfully recapitulates the NMR-derived structure information on 8 cyclic peptides. In contrast, OPLS-AA/M+TIP4P, Amber03+TIP3P, and Amber14SBonlysc+GB-neck2 could only recapitulate the NMR-derived structure information on 5 cyclic peptides, the majority of which are not well-structured.

This review explores the essential roles of purine metabolism including the catabolic product, uric acid, in the development of dopaminergic neurons of the substantia nigra pars compacta. The high energy requirements of the substantia nigra pars compacta alongside necessary purinergic neurotransmission and the influence of oxidative stress during development makes these neurons uniquely susceptible to changes in purine metabolism. Uric acid’s role as a central nervous system antioxidant may help to ameliorate these effects in utero. Understanding the mechanisms by which purines and uric acid influence development of the substantia nigra pars compacta can help further explain neurologic consequences of inborn errors of purine metabolism, such as Lesch–Nyhan disease.