MOLECULAR-DYNAMICS SIMULATIONS OF THE CONFORMATIONAL BEHAVIOR OF THE SYNTHETIC DIPEPTIDE PIDOTIMOD, A NEW IMMUNOSTIMULATING AGENT

Molecular dynamics (MD) simulations of the conformational behaviour of the conformers of PIDOTIMOD. an interleukin-2 lymphocyte T receptor a gonist dipeptide. have been carried out. MD simulations at constant te mperatures of 300 and 400 K and constant total energy runs at high tem peratures have been performed, and trajectories and statistical proper ties of motions investigated. At 300 K two trans and one cis conformer were found to be dynamically stable. Two puckered forms of the oxopro lyl ring in rapid equilibrium have been detected. The equilibrium conf ormations appear rather rigid and poor in H-bonds. At 400 K both trans and cis conformers are thermally mixed. At high temperatures large fl uctuations of the peptide bond between the oxo-prolyl and thyazolidin rings are observed. Nevertheless in the short time scale trans cis int erconversion does not occur. Suggestions on the nature of the structur e activity relationship are made.