COMPUTATIONAL STUDY OF THE CONFORMATIONAL PROFILES OF MODEL BIS-CYSTINE CYCLIC-PEPTIDES

Bis-cystine cyclic peptides are a new kind of molecules with potential use as cavitands, transporters or antagonists of target ligands. Stud ies aimed at establishing their conformational profiles may prove usef ul in understanding their characteristics and potentiate their use in molecular design. The present investigation reports the results of a c omputational study devoted to establishing the conformational preferen ces of model bis-cystine cyclic peptides and the properties in common with their linear analogs. For this purpose a study of four model comp ounds: (Ac-Cys-X-Cys-NHMe)(2) and (Ac-Cys-X-X-Cys-NHMe)(2) with X = Al a, Val, was performed. The goal of the study was to explore the import ance of the conformational nature of the central residues, the effect of the number of them, and the loss of conformational freedom after cy clization on model molecules. Accordingly, the conformational space an d the dynamic behaviour of the four cyclic peptides as well as the cor responding linear analogs was carefully explored. The results indicate the existence of structural patterns that might be useful for the use of this kind of molecule in de novo molecular design.