Hierarchical Cascades of Instability Govern the Mechanics of Coiled Coils: Helix Unfolding Precedes Coil Unzipping

摘要: Coiled coils are a fundamental emergent motif in proteins found structural biomaterials, consisting of α-helical secondary structures wrapped supercoil. A question regarding the thermal and mechanical stability coiled extreme environments is sequence events leading to disassembly individual oligomers from universal coiled-coil motifs. To shed light on this phenomenon, here we report atomistic simulations trimeric coil an explicit water solvent investigate mechanisms underlying helix unfolding unzipping assembly. We employ advanced sampling techniques involving steered molecular dynamics metadynamics obtain free-energy landscapes single-strand three-stranded Our comparative analysis instability pathways shows that sequential process multiple intermediates. At each intermediate state, one heptad repeat first unfolds then unzips due loss contacts with hydrophobic core. This observation suggests facilitates initiation disassembly, which confirmed by our 2D showing strand requires less energy unfolded state compared folded state. results explain recent experimental findings lay groundwork for studying hierarchical underpin thermomechanical stability/instability similar protein assemblies.