Predictive in silico all-atom folding of a four-helix protein with a free-energy model.
We report the predictive all-atom folding of the 60 amino acid four-helix bacterial ribosomal protein (BRP) L20 with a stochastic evolutionary optimization method in a free-energy force field. The energetically best, as well as six of the 10 lowest conformations, converge to a near-native structure. All of the 10 best energy conformations share the secondary structure elements of the native conformation, but differ in their tertiary alignment. The best conformation has a backbone root-mean-square deviation of 4.6 A to the native conformation and reproduces most distance constraints of the NMR experiment to 1.5 A resolution. Starting from random initial conditions, the native content of the simulated population increases more than 60-fold in the course of the simulation. These data demonstrate the feasibility of predictive unbiased all-atom protein folding with present day computational resources for the BRP L20.
Schug
Alexander
A
Forschungszentrum Karlsruhe, Institute for Nanotechnology, P.O. Box 3640, 76021 Karlsruhe, Germany.
Wenzel
Wolfgang
W
D001426:Bacterial Proteins / Q000737:chemistry*; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012269:Ribosomal Proteins / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
D001426:Bacterial Proteins; C040045:L20 ribosomal protein, bacteria; D012269:Ribosomal Proteins