PIDOTIMOD, A NEW IMMUNOSTIMULATING DIPEPTIDE, STUDIED BY MOLECULAR MECHANICS, NORMAL-MODE ANALYSIS AND DYNAMICS CALCULATIONS

A theoretical study of PIDOTIMOD, a new immunostimulating dipeptide, u sing a combination of molecular mechanics, normal mode analysis and dy namics methods, has been carried out. The results have been compared w ith the experimental ones obtained using NMR spectroscopy. Conformatio nal calculations and NMR spectra identify two classes of conformers, t rans and cis, around the peptide bond between the rings, with relative conformational populations of 0.55 and 0.45, respectively. The best a greement is obtained using a dielectric constant epsilon = 7 in the ca lculations. The conformational features show that the path connecting the trans and the cis forms may involve the rotation of the bridged pe ptide bond alone. From a dynamic point of view the conformers appear r ather rigid, and only the oxo-prolyl ring and the carboxyl group show significant rigid body-like motions. Interesting correlations occur in the fluctuations of the torsion angles.