MOLECULAR-DYNAMICS SIMULATIONS OF THE UNFOLDING OF AN ALPHA-HELICAL ANALOG OF RIBONUCLEASE-A S-PEPTIDE IN WATER

Molecular dynamics simulations of the S-peptide analogue AETAAAKFLREHMDS have been conducted in aqueous solution for 300 ps at 278 K and for 500 ps in two different runs at 358 K. The results show agreement with experimental observations in that at low temperature, 5-degrees-C, the helix is stable, while unfolding is observed at 85-degrees-C. In the low-temperature simulation a solvent-separated ion pair was formed between Glu-2 and Arg-10, and the side chain of His-12 reoriented toward the C-terminal end of the alpha-helix. Detailed analyses of the unfolding pathways at high temperature have also revealed that the formation or disappearance of main-chain helical hydrogen bonds occurs frequently through an alpha reversible 3(10) reversible no hydrogen bond sequence.