Stability and unfolding mechanism of the N-terminal β-hairpin from [2Fe-2S] ferredoxin I by molecular dynamics simulations

The stability and unfolding mechanism of the N-terminal β-hairpin of the [2Fe-2S] ferredoxin I from the blue-green alga Aphanothece sacrum in pure methanol, 40% (v/v) methanol-water, and pure water systems were investigated by 10 ns molecular dynamics simulations under periodic boundary conditions. The β-hairpin was mostly in its native-like state in pure methanol, whereas it unfolds dramatically following the 'zip-up' mechanism when it was placed in pure water. Both interstrand and inside-turn hydrogen bonds account for the stability of the β-hairpin in its native-like conformation, whereas hydrophobic interactions among nonpolar side chains are responsible for maintaining its stable loop-like intermediate structures in 40% (v/v) methanol-water. Reducing solvent polarity seems to increase the stability of the β-hairpin in its native-like structure. Methanol is likely to mimic the partially hydrophobic environment around the N-terminal β-hairpin by the subsequent α-helix.