CHARACTERIZATION OF THE SOLUTION CONFORMATION OF A CYCLIC RGD PEPTIDEANALOG BY NMR-SPECTROSCOPY ALLIED WITH A GENETIC ALGORITHM APPROACH AND CONSTRAINED MOLECULAR-DYNAMICS

The solution conformation of a cyclic RGD peptide analogue, oate-argin ine-glycine-asparlate-2-mercaptoanilide, has been determined via two i ndependent approaches for the searching of conformational space and id entification of conformations consistent with NMR and CD spectroscopic data: (i) the use of a binary genetic algorithm and (ii) a molecular dynamics simulation. Inter-proton distances were obtained via analysis of cross-peak volumes from a two-dimensional ROESY NMR spectroscopy e xperiment at 600 MHz and were used as constraints for the computationa l calculations. The mercaptoanilide amide proton resonance chemical sh ift had a very small temperature coefficient, indicating that this pro ton was hydrogen-bonded. Circular dichroism data showed that, in solut ion, the torsion angle about the disulfide bond was negative, consiste nt with one of the distinct conformations around this bond in the 200 ps molecular dynamics simulation. The backbone conformations of the st ructures resulting from the two different approaches were very similar . (C) Munksgaard 1994.