MOLECUI.AR PHARMACOLOOY. 39:51)251() Theoretical Study of the Flexibility and Solution Conformation of the Cyclic Opioid Peptides [DPen2,D-Pen5]Enkephalin and [D-

An investigation of the conformational profiles of two cyclic #{244}-selective opioid peptides, [D-Pen2,D-Pen5]-enkephalin and [D-Pen2,L-Pen5]-enkephalin, has been made. The methods and pro-cedures used are more extensive and systematic than those previously reported, involving a combination of nested grid ro-tations, cyclic ring-closing algorithms, molecular dynamic simu-lations at high and low temperature, and total geometry optimi-zations. The reexamination is a necessary first step in further characterization of the bioactive form of -seIective peptides. This study also addresses the question of how rigid such cyclic analogs actually are. Finally, the effect of solvent environment on the low energy conformers obtained from the extensive search strategy has been determined. Simulation of the effect of water as a solvent by a continuum dielectric constant of 80 results in the breaking of internal hydrogen bonds and re