How fast-folding proteins fold.
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 nativelike 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.
D. E. Shaw Research, New York, NY 10036, USA. kresten.lindorff-larsen@DEShawResearch.com
Kresten
K
Lindorff-Larsen
Stefano
S
Piana
Ron O
RO
Dror
David E
DE
Shaw
D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D011506:Proteins