Determining the Energetics of Small β-Sheet Peptides using Adaptive Steered Molecular Dynamics.

Mechanically driven unfolding is a useful computational tool for extracting the energetics and stretching pathway of peptides. In this work, two representative β-hairpin peptides, chignolin (PDB: 1UAO ) and trpzip1 (PDB: 1LE0 ), were investigated using an adaptive variant of the original steered molecular dynamics method called adaptive steered molecular dynamics (ASMD). The ASMD method makes it possible to perform energetic calculations on increasingly complex biological systems. Although the two peptides are similar in length and have similar secondary structures, their unfolding energetics are quite different. The hydrogen bonding profile and specific residue pair interaction energies provide insight into the differing stabilities of these peptides and reveal which of the pairs provides the most significant stabilization.