One-dimensional barrier-preserving free-energy projections of a beta-sheet miniprotein: new insights into the folding process.

One-Dimensional Barrier Preserving Free-Energy Projections of a β-sheet Miniprotein: New Insights into the Folding Process SUPPLEMENTARY MATERIAL

New insights into the folding of a β-sheet miniprotein in a reduced space of collective hydrogen bond variables: application to a hydrodynamic analysis of the folding flow.

A new analysis of the 20 μs equilibrium folding/unfolding molecular dynamics simulations of the three-stranded antiparallel β-sheet miniprotein (beta3s) in implicit solvent is presented. The conformation space is reduced in dimensionality by introduction of linear combinations of hydrogen bond distances as the collective variables making use of a specially adapted principal component analysis (...

Delineation of folding pathways of a β-sheet miniprotein.

Several methods have been developed in the past few years for the analysis of molecular dynamics simulations of biological (macro)molecules whose complexity is difficult to capture by simple projections of the free-energy surface onto one or two geometric variables. The locally scaled diffusion map (LSDMap) method is a nonlinear dimensionality reduction technique for describing the dynamics of ...

Identification of the protein folding transition state from molecular dynamics trajectories.

The rate of protein folding is governed by the transition state so that a detailed characterization of its structure is essential for understanding the folding process. In vitro experiments have provided a coarse-grained description of the folding transition state ensemble (TSE) of small proteins. Atomistic details could be obtained by molecular dynamics (MD) simulations but it is not straightf...

Kinetic analysis of molecular dynamics simulations reveals changes in the denatured state and switch of folding pathways upon single-point mutation of a beta-sheet miniprotein.

The effects of a single-point mutation on folding thermodynamics and kinetics are usually interpreted by focusing on the native structure and the transition state. Here, the entire conformational spaces of a 20-residue three-stranded antiparallel beta-sheet peptide (double hairpin) and of its single-point mutant W10V are sampled close to the melting temperature by equilibrium folding-unfolding ...