Journal Article

How Fast-Folding Proteins Fold

Shaw, David E., Dror, Ron O., Piana, Stefano, Lindorff-Larsen, Kresten

2011

Overview

An outstanding challenge in the field of molecular biology has been to understand the process by which proteins fold into their characteristic three-dimensional structures. Here, we report the results of atomic-level molecular dynamics simulations, over periods ranging between 100 µs and 1 ms, that reveal a set of common principles underlying the folding of 12 structurally diverse proteins. In simulations conducted with a single physics-based energy function, the proteins, representing all three major structural classes, spontaneously and repeatedly fold to their experimentally determined native structures. Early in the folding process, the protein backbone adopts a n ative like topology while certain secondary structure elements and a small number of nonlocal contacts form. In most cases, folding follows a single dominant route in which elements of the native structure appear in an order highly correlated with their propensity to form in the unfolded state.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Amino acids / Biological and medical sciences / Conformational dynamics in molecular biology / Coordinate systems / energy / Experimental methods / Force field / Fundamental and applied biological sciences. Psychology / Kinetics / Molecular biology / Molecular biophysics / Molecular dynamics / Molecular Dynamics Simulation / Molecular structure / Protein Conformation / Protein Folding / Protein Structure, Secondary / Proteins / Proteins - chemistry / Signal transduction / Structural members / Thermodynamics / Time series / Topology