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The equilibrium properties and folding kinetics of an all-atom model of the Trp-cage
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10.1063/1.1874812
/content/aip/journal/jcp/122/11/10.1063/1.1874812
http://aip.metastore.ingenta.com/content/aip/journal/jcp/122/11/10.1063/1.1874812
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Figures

Image of FIG. 1.
FIG. 1.

(a) Ribbon representation of the global minimum structure of an all-atom off-lattice model of fragment of the Trp-cage. Residues Tyr-3, Trp-6, Asp-9, Arg-16, Pro-17, Pro-18, and Pro-19 are shown in atomic details. The following features are labeled: helix, residue Trp-6, the Asp-9-Arg-l6 salt bridge, and the helix. Drawn using molscript (Ref. 87) (b) The native residue-residue contact map of the model Trp-cage. The native tertiary contacts and native secondary-structure hydrogen bonds are above and below the diagonal, respectively. A residue-residue pair is in contact if there is at least one square-well atomic contact between them.

Image of FIG. 2.
FIG. 2.

(a) Reduced heat capacity as a function of the reduced temperature . The data points and error bars are averages obtained from the five simulation runs at each temperature. The curve is obtained from the weighted histogram method (Ref. 75). (b) Probability distribution at the transition temperature obtained by the weighted histogram method.

Image of FIG. 3.
FIG. 3.

rmsd vs reduced time plot of an equilibrium simulation at the transition temperature . The rmsd is the root-mean-square deviation of a Trp-cage structure from the global minimum native structure of the Trp-cage model.

Image of FIG. 4.
FIG. 4.

Probability distribution as a function of rmsd and the fraction of nonlocal contacts . (a) Equilibrium simulations at of wild-type Trp-cage. The vicinities of the native state, transition state TS, and coil state are indicated. Regions where contour lines are closely spaced indicate steep changes in the probability distribution. The very dark region corresponds to a sharp peak about the native state; (b) Folding simulations at of the wild-type Trp-cage, with the calculated TS region indicated. The salt-bridge intermediate state is indicated by ; (c) Folding simulations at of the wild-type Trp-cage, with the calculated TS region indicated; (d) Folding simulations at of the mutated Trp-cage.

Image of FIG. 5.
FIG. 5.

Folding of a Trp-cage at by a category 1 mechanism: (a) , random coil without any secondary or tertiary structure; (b) , partial helix; (c) , initial core contacts; (d) , stabilization of helix; (e) , increase in core contacts and appearance of helix; (f) , folded protein.

Image of FIG. 6.
FIG. 6.

rmsd vs reduced time plots of folding simulations: (a) category 1, early -helix formation, followed by fluctuating core contacts, before folding to the native state; (b) category 1, early -helix formation, followed by core contacts, which rapidly leads to folding to the native state; (c) category 2, early formation of the Trp-cage core, followed by the slow and gradual reorganization of secondary structure, which eventually leads to the native state. The approximate time of the occurrences of the transition states are indicated by “TS” in the graphs.

Image of FIG. 7.
FIG. 7.

A snapshot of a Trp-cage folding simulation that folds by a category 2 mechanism, in which partial Trp-cage core contacts occur before -helix formation. The main-chain carbonyl oxygen (in red) of residue Leu-2 and the main-chain amine hydrogen (in white) of residue Trp-6 are enlarged and marked to illustrate the structural frustration.

Image of FIG. 8.
FIG. 8.

Folding of a Trp-cage at by a category 2 mechanism: (a) , early core formation; (b) , -helical structure on the -terminal side; (c) , increase in core and -helical structure; (d) , folded structure.

Image of FIG. 9.
FIG. 9.

(a) Average contact map of the kinetic intermediate I state, obtained from 383 conformation with reaction coordinates and ; (b) A ribbon diagram of one of the conformations, with the Asp-9-Arg-16 salt bridge indicated.

Image of FIG. 10.
FIG. 10.

Probability of nonlocal residue-residue contacts of the 100 folding trajectories at . Residue-residue contacts and secondary-structure hydrogen bonds are above and below the diagonal, respectively. (a) , (b) , (c) , (d) , (e) , and (f) . Cross symbol denotes a contact probability in the range of 0.1–0.2; open circle 0.2–0.4; star 0.4–0.6; filled triangle 0.6–0.8; filled square 0.8–1.

Image of FIG. 11.
FIG. 11.

Probability of nonlocal residue-residue contacts of the 100 folding trajectories at . Residue-residue contacts and secondary-structure hydrogen bonds are above and below the diagonal, respectively. (a) , (b) , (c) , (d) , (e) , and (f) . Cross symbol denotes a contact probability in the range of 0.1–0.2; open circle 0.2–0.4; star 0.4–0.6; filled triangle 0.6–0.8; filled square 0.8–1.

Image of FIG. 12.
FIG. 12.

(a) Average contact map of the 31 transition state conformations at . (b) A ribbon diagram of one of the 31 transition state structures at . (c) Average contact map of the 37 transition state conformations at . (d) A ribbon diagram of one of the 37 transition state structures at .

Image of FIG. 13.
FIG. 13.

Reduced free energy vs rmsd plots at and 3.6. The reduced free energy is defined by the usual statistical mechanical method (Ref. 88) as (rmsd), where (rmsd) is the unnormalized population distribution over the reaction coordinate rmsd.

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/content/aip/journal/jcp/122/11/10.1063/1.1874812
2005-03-17
2014-04-23
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752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd
Scitation: The equilibrium properties and folding kinetics of an all-atom Go¯ model of the Trp-cage
http://aip.metastore.ingenta.com/content/aip/journal/jcp/122/11/10.1063/1.1874812
10.1063/1.1874812
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