Reversible folding/unfolding of small a-helix in explicit solvent investigated by ABEEMσπ/MM

Abstract

We have performed molecular dynamics simulations on the reversible folding/unfolding of small α-helix (short Ala based peptide Ala5) in explicit water solvent in terms of ABEEMσπ/MM. A dynamics analysis shows that the α-helical turn can be preserved up to a period of about 2 ns at 300 K, which supports the conclusions of Margulis et al. The time trajectory of the root mean square deviation between the heavy atoms of the backbone and the helical reference structure indicate that “helix melting and formation occurs rapidly on a time scale of 0.1 ns at 300 K” is not a felicitous conclusion. We first quantificationally concluded that the helix nucleation can maintain 2 ns, 1–1.5 ns and 0.8 ns for Ala5 at 300 K, 400 K and 500 K, respectively. Furthermore, increasing temperature dose not alter the pathway of folding/unfolding, but change the rate. An analysis of structures in a “transition-state ensemble” shows that helix-to-coil transitions occurs predominantly through breaking of hydrogen bonds at the helix ends (92%), particularly at the C-terminus(50%). Hydrogen bonds’ breaking and formation occurs on a time scale of 0.1 ns.