1887
banner image
No data available.
Please log in to see this content.
You have no subscription access to this content.
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.
Simple estimation of absolute free energies for biomolecules
Rent:
Rent this article for
USD
10.1063/1.2174008
/content/aip/journal/jcp/124/10/10.1063/1.2174008
http://aip.metastore.ingenta.com/content/aip/journal/jcp/124/10/10.1063/1.2174008

Figures

Image of FIG. 1.
FIG. 1.

Depiction of how the reference potential energy is calculated for a one-coordinate system. First the coordinate is binned, creating a histogram (solid bars) populated according to a simulation. Then Eq. (4) is used to calculate reference energies for each coordinate bin (dashed bars). A hypothetical physical potential is shown as a dotted curve for comparison to . For a multicoordinate system would be the sum of the single-coordinate reference potential energies.

Image of FIG. 2.
FIG. 2.

Absolute free energy for methane estimated by the reference system method as a function of the number of reference structures used in the estimate. The solid horizontal line is the exact free energy obtained by numerical integration. Five independent simulations are shown on a log scale to clearly show the convergence of the free energy estimate. The results shown were obtained using Eq. (10) with 100 bins for each degree of freedom, i.e., the estimates for the absolute free energy of methane in Table I are the values shown here for .

Image of FIG. 3.
FIG. 3.

Absolute free energy for methane estimated by the reference system method as a function of the number of histogram bins used for each degree of freedom. The plot shows the “sweet spot” where histogram bins are small enough to reveal histogram features, yet large enough to give sufficient population in each bin. The results are shown with a vertical scale of and on a log scale to emphasize the wide range of bin sizes that produce excellent results for the reference system approach. The results shown were obtained using Eq. (10) for a methane molecule using (dashed curve) and (solid curve). The solid horizontal line shows the exact free energy and the error bars are the standard deviations of five independent trials. The plot demonstrates that at least 50 bins should be used for each independent coordinate and that the maximum number of bins depends on the number of snapshots in the physical ensemble.

Image of FIG. 4.
FIG. 4.

Free energy for leucine dipeptide estimated by the reference system method as a function of the number of reference structures used in the estimate. Five independent simulations are shown on a log scale to demonstrate the convergence behavior of the free energy estimate for (a) the alpha configuration and (b) the beta configuration. The results shown were obtained using Eq. (10) with 50 bins for each degree of freedom.

Image of FIG. 5.
FIG. 5.

Scatter plots of the two torsions of each residue for leucine dipeptide. The results are shown for both physical and reference ensembles containing 100 000 structures each. The figure shows that (i) the reference system has good overlap with the physical system, as can be seen by the similarity between the two plots, and (ii) the reference system is more broadly distributed than the physical system, as evidenced by the data at for the reference system that is not present for the physical system.

Image of FIG. 6.
FIG. 6.

Histogram of the distance between the of residue 1 and the of residue 2 for leucine dipeptide. The results are shown for both reference and physical ensembles containing 100 000 structures each. The figure shows that (i) the reference system has good overlap with the physical system and (ii) the reference system is broader than the physical system.

Tables

Generic image for table
Table I.

Absolute free energy estimates obtained using our reference system approach for cases where the absolute free energy can be determined exactly. In all cases, the estimate is in excellent agreement with the exact free energy. The uncertainty, shown in parentheses [e.g., 3.14 ] is the standard deviation from five independent simulations. The results for the two-dimensional systems are in units and methane results have units of kcal/mole. The table shows estimates of the configurational integral in Eq. (2), i.e., the constant term is not included in the estimate.

Generic image for table
Table II.

Absolute free energy estimates of the alpha and beta conformations obtained using the reference system method for leucine dipeptide with GBSA solvation, in units of kcal/mol. The independent measurement for the free energy difference was obtained via a unconstrained simulation. The uncertainty for the absolute free energies, shown in parentheses, is the standard deviation from five independent leucine dipeptide simulations using reference structures in the reference ensemble. The uncertainty for the free energy differences is obtained by using every possible combination of and , i.e., 25 independent estimates. The standard error associated with the reference system estimate is , reflecting the 25 independent estimates. The table shows estimates of the configurational integral in Eq. (2), i.e., the constant term is not included in the estimate.

Loading

Article metrics loading...

/content/aip/journal/jcp/124/10/10.1063/1.2174008
2006-03-10
2014-04-20
Loading

Full text loading...

This is a required field
Please enter a valid email address
752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd
Scitation: Simple estimation of absolute free energies for biomolecules
http://aip.metastore.ingenta.com/content/aip/journal/jcp/124/10/10.1063/1.2174008
10.1063/1.2174008
SEARCH_EXPAND_ITEM