Conformational energy studies of oxytocin and its cyclic moiety.

Conformational energies were calculated for oxytocin in water, starting with a conformation proposed from nuclear magnetic resonance measurements in [U-(2)H](CH(3))(2)SO. Calculations on the isolated ring showed that conformations with one transannular hydrogen bond had the same energies as those without such bonds; those with two such hydrogen bonds do not appear to form. Calculations on the whole molecule also indicated the existence of several low-energy minima in the energy surface, and no preference for hydrogen-bond formation in the cyclic moiety; the hydrogen bond proposed between the Gly peptide NH and the Cys-6 C=O in the acyclic moiety can form. The proposed proximity of the tail to the ring is one of two low-energy conformations found. The Tyr side chain had two conformations of comparable energy, one over the ring between the Gln and Asn side chains, and the other with the Tyr side chain away from the ring. The oxytocin molecule appears to be flexible, and is probably sensitive to changes in its environment.