Zipper-Like Unfolding of β-Sheets Accessed by Pioneer Water Molecules: Atomic Resolution of Forced Unfold Reveals Different Mechanisms for Parallel and Antiparallel Motifs

In this study, quantum mechanical calculations were used for an atomic level investigation of the β-sheet unfolding mechanism aided by pioneer water molecules accessing the structural motif. Results indicate that there is a qualitatively different forced unfold mechanism for parallel and antiparallel β-sheets. In the case of parallel β-sheets, the presence of only a single water molecule could already be enough to stimulate rupture of consecutive backbone hydrogen bonds by stepping from one H-bond to the next one, similarly as a slider opens up a zipper. The extension curves and energetics obtained at the B3LYP/6-311++G(d,p)//B3LYP/6-31G(d) level of theory correlate well and may explain the hyperfine resolution of experimentally observed sawtooth patterns in single molecule studies where external pulling force was applied.