Conformational Energy Calculations on the Eosinophil Chemotactic Peptide Analog Val-Gly-Ala-Glu: Comparison of Theory and Experiment

Conformational energy calculations have been employed to obtain minimum energy conformations of the peptide Val- Gly-Ala-Glu , an analogue of eosinophil chemotactic tetrapeptides. The calculated conformations of the peptide can be described as an ensemble of structures in which the C-terminal and N-terminal regions of the molecule are in close proximity. The charge state of the peptide showed a marked effect on the calculated conformation, and the results were also sensitive to the electrostatic environment. The calculations performed on the dianionic form of the molecule showed good agreement with experimental n.m.r . Data on coupling constants, amide-proton resonance chemical shifts and temperature coefficients, nuclear Overhauser effects, side-chain rotamer populations, and binding of paramagnetic ions, obtained in dimethyl sulfoxide solutions. The calculations demonstrate some of the inherent problems facing theoretical calculations of peptide structure.