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Computing conformational free energy by deactivated morphing
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10.1063/1.2982170
/content/aip/journal/jcp/129/13/10.1063/1.2982170
http://aip.metastore.ingenta.com/content/aip/journal/jcp/129/13/10.1063/1.2982170

Figures

Image of FIG. 1.
FIG. 1.

DM. An ensemble around conformation A is gradually transformed into another ensemble around conformation B through restraining, deactivating, and morphing. Dashed circles represent position restraints. Often, intermediate states are required in some or all of the steps.

Image of FIG. 2.
FIG. 2.

Four conformations of AlaD selected from the map. The four circles roughly correspond to the boundaries of the basins within RMSD from the four reference conformations. The free-energy map was constructed from an umbrella sampling simulation using 144 windows spaced every in and . For each window, we collected data from a 750 ps run after a 250 ps equilibration period.

Image of FIG. 3.
FIG. 3.

Simulation box containing an AlaD molecule and 275 water molecules.

Image of FIG. 4.
FIG. 4.

Overlap of states in the restraining procedure for AlaD. Each panel contains 15 distributions of from the reference conformation, A, B, C, and D, for 15 different restraining states, (from left to right). The spring constants are , 600, 360, 216, 129.6, 77.76, 46.66, 27.99, 16.80, 10.08, 6.05, 3.63, 2.18, 1.31, and .

Image of FIG. 5.
FIG. 5.

Outcome of DM applied to the four conformations of AlaD. The numbers next to arrows denote the free-energy differences (in kcal/mol) associated with the transitions. The numbers next to dashed arrows are the total free-energy differences between the conformation ensembles. The numbers in parentheses are the simulation time (in nanosecond) used to compute the free-energy differences. The free-energy difference between Q and M, denoted by , cancels out exactly.

Image of FIG. 6.
FIG. 6.

Two conformations of Ala10: helix and hairpin.

Image of FIG. 7.
FIG. 7.

Simulation box containing an Ala10 molecule and 676 water molecules.

Image of FIG. 8.
FIG. 8.

Overlap of states in the restraining procedure for Ala10. Each panel contains 30 distributions of from the reference conformation, helix and hairpin, for 30 different restraining states, (from left to right). The spring constants are , 700, 490, 343, 240.1, 168.07, 117.65, 82.35, 57.65, 40.35, 28.25, 19.77, 13.84, 9.69, 6.78, 4.75, 3.32, 2.33, 1.63, 1.14, 0.80, 0.56, 0.39, 0.27, 0.19, 0.13, 0.09, 0.07, 0.05, and .

Image of FIG. 9.
FIG. 9.

Morphing between helix and hairpin. The free-energy profile over the course of morphing is shown as a function of the parameter in Eq. (11). Of 51 conformations used, six are shown. Meshes represent molecular surfaces, and red tubes are traces of backbone.

Image of FIG. 10.
FIG. 10.

Outcome of DM applied to the helix (a) and hairpin (b) conformations of Ala10. The numbers next to arrows denote the free-energy differences (in kcal/mol) associated with the transitions. The number next to the dashed arrow is the total free-energy difference between the two conformation ensembles. The numbers in parentheses are the simulation time (in nanosecond) used to compute the free-energy differences. The free-energy difference between Q and M, denoted by , cancels out exactly.

Image of FIG. 11.
FIG. 11.

Dependence of the free-energy difference on the RMSD cutoff.

Tables

Generic image for table
Table I.

Protein energy and deactivation free energy (in kcal/mol). The numbers in parentheses are the relative values, with conformation A as a reference.

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/content/aip/journal/jcp/129/13/10.1063/1.2982170
2008-10-01
2014-04-24
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752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd
Scitation: Computing conformational free energy by deactivated morphing
http://aip.metastore.ingenta.com/content/aip/journal/jcp/129/13/10.1063/1.2982170
10.1063/1.2982170
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