In silico folding of a three helix protein and characterization of its free-energy landscape in an all-atom force field.

@article{Herges2005InSF,
  title={In silico folding of a three helix protein and characterization of its free-energy landscape in an all-atom force field.},
  author={Thomas Herges and Wolfgang Wenzel},
  journal={Physical review letters},
  year={2005},
  volume={94 1},
  pages={
          018101
        }
}
  • T. Herges, W. Wenzel
  • Published 29 October 2003
  • Chemistry, Physics, Medicine, Biology
  • Physical review letters
We report the reproducible first-principles folding of the 40 amino-acid, three-helix headpiece of the HIV accessory protein in a recently developed all-atom free-energy force field. Six of 20 simulations using an adapted basin-hopping method converged to better than 3 A backbone rms deviation to the experimental structure. Using over 60 000 low-energy conformations of this protein, we constructed a decoy tree that completely characterizes its folding funnel. 

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References

SHOWING 1-10 OF 73 REFERENCES
Reproducible protein folding with the stochastic tunneling method.
TLDR
A novel version of the stochastic tunneling method and a recently developed all-atom protein free-energy force field are used to reproduce the reproducible folding of the 20 amino-acid protein trp cage. Expand
An all-atom force field for tertiary structure prediction of helical proteins.
TLDR
An all-atom free-energy force field (PFF01) is developed for protein tertiary structure prediction and validated for five nonhomologous helical proteins with 20-60 amino acids. Expand
All-atom structure prediction and folding simulations of a stable protein.
TLDR
Results are presented from all-atom, fully unrestrained ab initio folding simulations for a stable protein with nontrivial secondary structure elements and a hydrophobic core that is currently the smallest protein that displays two-state folding properties. Expand
Solvation energy in protein folding and binding
TLDR
A method for calculating the stability in water of protein structures, starting from their atomic coordinates, as the product of the accessibility of the atom to solvent and its atomic solvation parameter is developed. Expand
Folding a protein in a computer: An atomic description of the folding/unfolding of protein A
  • A. Garcia, J. Onuchic
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2003
TLDR
The folding mechanism of a three-helix bundle protein is studied at atomic resolution, including effects of explicit water, and the kinetic bottlenecks for folding can be determined from the thermal ensembles of structures on the free energy barriers, provided the kinetically determined transition-state ensembled are similar to those determined fromfree energy barriers. Expand
Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution.
An implementation of classical molecular dynamics on parallel computers of increased efficiency has enabled a simulation of protein folding with explicit representation of water for 1 microsecond,Expand
Recent improvements in prediction of protein structure by global optimization of a potential energy function
TLDR
The resulting lowest-energy structures of the target proteins agreed with the experimental structures in many respects and constitute an important step toward the ab initio prediction of protein structure solely from the amino acid sequence. Expand
Easily searched protein folding potentials.
  • G. Crippen
  • Chemistry, Medicine
  • Journal of molecular biology
  • 1996
TLDR
A method for accurately recovering the given contact potential from only a knowledge of which sequences fold to which structures and what the non-native structures are and how to derive from the same information more general potential functions having much better positive correlations between potential function value and conformational deviation from the native. Expand
Folding funnels: The key to robust protein structure prediction
TLDR
The optimization procedure is outlined in the context of associative memory energy functions originally introduced for tertiary structure recognition and it is demonstrated that even partially funneled landscapes lead to qualitatively correct, low‐resolution predictions. Expand
Theory of protein folding: the energy landscape perspective.
TLDR
The energy landscape theory of protein folding suggests that the most realistic model of a protein is a minimally frustrated heteropolymer with a rugged funnel-like landscape biased toward the native structure. Expand
...
1
2
3
4
5
...