Comparative conformational analysis of [D-Pen2,D-Pen5]enkephalin (DPDPE): a molecular mechanics study.

A theoretical conformational analysis (molecular mechanics study) of the delta opioid receptor-selective enkephalin analog H-Tyr-D-Pen-Gly-Phe-D-Pen-OH (DPDPE) was performed, based on the use of the SYBYL software. The study led to the identification of several conformers that were significantly lower in energy than previously reported candidate conformers of DPDPE which, for comparative purposes, were also minimized by using the standard SYBYL force field. The results revealed a considerable degree of conformational flexibility of the DPDPE molecule, and suggested that incorporation of further conformational constraints into this enkephalin analog will be necessary in order to elucidate its receptor-bound conformation.