Adaptive Steered Molecular Dynamics: Unfolding of Neuropeptide Y and Decaalanine Stretching

Abstract

The energetics of an unfolding event can be obtained using steered molecular dynamics (SMD) and Jarzynski's inequality with the cost of the calculation increasing dramatically with the length of the path. An adaptive algorithm has been introduced∗ that allows for the path to be nonlinear and staged while reducing the computational cost. The potential of mean force (PMF) obtained for neuropeptide Y (NPY) in water along an unfolding path confirmed that the monomeric form of NPY adopts the pancreatic-polypeptide (PP) fold. Adaptive SMD can also be used to reconstruct the PMF obtained earlier for stretching decaalanine in vacuum# at lower computational cost. The PMF for stretching decaalanine in water solvent (using the TIP3P water potential) at 300K has now been obtained using adaptive SMD. Not surprisingly, the stabilization from the water solvent reduces the overall work required to unfold it. However, the PMF remains structured suggesting that some regions of the energy landscape act partially as doorways.∗G. Ozer, E. Valeev, S. Quirk and R. Hernandez, J. Chem. Theory Comput. (2010), doi:10.1021/ct100320g.#S. Park and K. Schulten, J. Chem. Phys.120, 5946 (2004).View Large Image | View Hi-Res Image | Download PowerPoint Slide