Fig. 1.

Chemical structures of labeled compounds and their molecular dynamic profiling for assessing ligand mobility. (A) Heterobivalent ligands containing melanocortin (brown) and cholecystokinin (green) pharamacophores connected via a PEGO-[PG]₃-PEGO linker (cyan) that bears a lysine handle for incorporation of Cy5 and Eu-DTPA tags (blue). (B–D) Molecular dynamic study of Cy5 labeled ligand 1 (htMVL 1). (B) Illustration of one of the conformers with various functionalities and atom labels that were monitored for distances during the simulation is shown in C, and energy plot of various conformations (distance mapped from atoms 48–496) against temperature is shown in D. The study reveals significant linker mobility with 30–70 Å spacing between the two motifs and an average distance range of 40 Å (see SI Materials and Methods for more details).