Investigation of Methanol–Peptide Nuclear Overhauser Effects through Molecular Dynamics Simulations

Intermolecular nuclear Overhauser effects (NOEs) produced by interactions of methanol with [val5]angiotensin in 25% methanol–water at 0 °C were examined through molecular dynamics (MD) simulations and compared to experimental results. Calculated average 3JNHCαH spin coupling constants, conformation-sensitive chemical shift changes, and intramolecular 1H–1H NOEs indicated that peptide conformations present over the course of simulation trajectories of 100–300 ns are likely similar to those present in the experimental system. Calculated cross-relaxation terms for the methanol–peptide interactions showed the same trends as corresponding experimental data but were about a factor of 3 too large. The lack of agreement between observed and calculated cross-relaxation terms probably has origins in characteristics of the simulations that lead to overestimation of translational diffusion coefficients of the system components. Simulations confirmed the heterogeneity of the methanol–water solvent at the molecular lev...