Acetyl-(D) Arginyl - Glycyl- (D) Aspartic Acid Is A Better Integrin Binding Analog Than Acetyl - Arginyl - Glycyl-Aspartic Acid In Membrane Mimicking Solvents

Using molecular dynamics simulations and nuclear magnetic resonance techniques we explored the conformational preferences of linear and chiral analogs of acetyl-arginyl-glycyl-aspartic acid (Ac-RGD) and acetyl-arginyl--Alanyl-aspartic acid (Ac-RXD). Using tinker molecular modeling program and 5nano second molecular dynamics simulations in water/dimethyl sulphoxide to mimic the varying environment experienced by the peptide from water to membrane/dimethyl sulphoxide-d6, in trans-cellular transport process. We validate the simulation results with the complementary nuclear magnetic resonance experiments. Results from both the techniques suggest that the Acetyl-(d)arginyl-glycyl-(d)aspartic acid is more susceptible for integrin binding than that of Ac-RGD. This is because more number of conformations was found to be fit with the pseudo-dihedral angle with −45° ≤ pdo ≤ +45°, an essential criterion for integrin binding and with valid interatomic distances in both the solvent conditions, laid down by various researchers. This peptide is stabilized by Arg-NH ... O=C-Asp hydrogen bonding interaction in dimethyl sulphoxide-d6. Results from pseudodihedral angle and inter atomic distances of unusual -Alanine analogs acetyl-arginyl--alanyl-aspartic acid suggest that the more number of conformers of this peptide is found to be fit in the pseudo-dihedral angle criteria than the other chiral analog except Ac-RGD and Ac-rGd. There is a good correlation between simulation and NMR experimental results.