Theoretical studies of the amide I vibrational frequencies of [Leu]-enkephalin

Abstract

DFT vibrational frequency calculations on conformers of trans-N-methylacetamide + D₂O clusters, and various dipeptides were used to parameterize a seven-site model for predicting the diagonal force constants of the amide I mode of arbitrary polypeptides at the EDF1/6-31+G* level. The ultimate aim of the work is to improve the accuracy of the simple ‘floating-oscillator’ method for calculating the amide I band profiles of proteins. The model describes hydrogen-bonded and distant interactions correctly, but short-range bonded effects are not well reproduced. We therefore suggest the use of a combination of lookup tables for local interactions and the seven-site model for the remainder. To test the model, we determined the vibrational frequencies of the low energy conformers of the pentapeptide, [Leu]-enkephalin at the EDF1/6-31+G* level. The model reproduced the DFT diagonal force constants well.

Acknowledgement

We thank the EPSRC for a Biomolecular Sciences PhD studentship for TMW and a JREI grant (GR/62052/01) for a computer cluster. We also thank Dr Nick Besley (University of Nottingham), Dr Lavina Snoek and Professor John Simons (Oxford University) for fruitful discussions.