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Replica exchange improves sampling in low-resolution docking stage of RosettaDock.

Zhang Z, Lange OF - PLoS ONE (2013)

Bottom Line: A benchmark of 30 complexes starting from structures of the unbound binding partners shows improved performance for ReplicaDock and ZDOCK when compared to shotgun sampling at equal or less computational expense.ReplicaDock and ZDOCK consistently reach lower energies and generate significantly more near-native conformations than shotgun sampling.Additionally, the refined ReplicaDock ensembles reach significantly lower interface energies and many previously hidden features of the docking energy landscape become visible when ReplicaDock is applied.

View Article: PubMed Central - PubMed

Affiliation: Biomolecular NMR and Munich Center for Integrated Protein Science, Department Chemie, Technische Universität München, Garching, Germany.

ABSTRACT
Many protein-protein docking protocols are based on a shotgun approach, in which thousands of independent random-start trajectories minimize the rigid-body degrees of freedom. Another strategy is enumerative sampling as used in ZDOCK. Here, we introduce an alternative strategy, ReplicaDock, using a small number of long trajectories of temperature replica exchange. We compare replica exchange sampling as low-resolution stage of RosettaDock with RosettaDock's original shotgun sampling as well as with ZDOCK. A benchmark of 30 complexes starting from structures of the unbound binding partners shows improved performance for ReplicaDock and ZDOCK when compared to shotgun sampling at equal or less computational expense. ReplicaDock and ZDOCK consistently reach lower energies and generate significantly more near-native conformations than shotgun sampling. Accordingly, they both improve typical metrics of prediction quality of complex structures after refinement. Additionally, the refined ReplicaDock ensembles reach significantly lower interface energies and many previously hidden features of the docking energy landscape become visible when ReplicaDock is applied.

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Detailed analysis of shotgun and ReplicaDock sampling on target 1ppf.A) energy distribution of shotgun sampling generated low-resolution decoys. B) energy distribution of conformations sampled by ReplicaDock at respective inverse temperatures. C–F) Population of sampled conformations in spherical coordinates. Partner A is fixed at the center and the position of Partner B with respect to an idealized spherical surface around Partner A is recorded. The native structure is labeled as white dot (arrow in C). G–J) Conformations are assigned to grid-cells as in C–F, but shown is the lowest energy of all conformations assigned to the respective grid cell. The same color-scale is used for each plot of a row, and the colorbars are attached to the rightmost panel.
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pone-0072096-g002: Detailed analysis of shotgun and ReplicaDock sampling on target 1ppf.A) energy distribution of shotgun sampling generated low-resolution decoys. B) energy distribution of conformations sampled by ReplicaDock at respective inverse temperatures. C–F) Population of sampled conformations in spherical coordinates. Partner A is fixed at the center and the position of Partner B with respect to an idealized spherical surface around Partner A is recorded. The native structure is labeled as white dot (arrow in C). G–J) Conformations are assigned to grid-cells as in C–F, but shown is the lowest energy of all conformations assigned to the respective grid cell. The same color-scale is used for each plot of a row, and the colorbars are attached to the rightmost panel.

Mentions: The short Monte-Carlo sampling explores only a small region of conformational space around the respective starting position, which is reflected by a strong correlation between I_rms to the native complex structure before and after the Monte Carlo optimization (Figure 1A). Thus, the generated ensemble of structures is highly biased by the initial starting structures, rather than by the low-resolution energy (Figure 2C+G; Figure S4C+G in Supporting Information S1).


Replica exchange improves sampling in low-resolution docking stage of RosettaDock.

Zhang Z, Lange OF - PLoS ONE (2013)

Detailed analysis of shotgun and ReplicaDock sampling on target 1ppf.A) energy distribution of shotgun sampling generated low-resolution decoys. B) energy distribution of conformations sampled by ReplicaDock at respective inverse temperatures. C–F) Population of sampled conformations in spherical coordinates. Partner A is fixed at the center and the position of Partner B with respect to an idealized spherical surface around Partner A is recorded. The native structure is labeled as white dot (arrow in C). G–J) Conformations are assigned to grid-cells as in C–F, but shown is the lowest energy of all conformations assigned to the respective grid cell. The same color-scale is used for each plot of a row, and the colorbars are attached to the rightmost panel.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3756964&req=5

pone-0072096-g002: Detailed analysis of shotgun and ReplicaDock sampling on target 1ppf.A) energy distribution of shotgun sampling generated low-resolution decoys. B) energy distribution of conformations sampled by ReplicaDock at respective inverse temperatures. C–F) Population of sampled conformations in spherical coordinates. Partner A is fixed at the center and the position of Partner B with respect to an idealized spherical surface around Partner A is recorded. The native structure is labeled as white dot (arrow in C). G–J) Conformations are assigned to grid-cells as in C–F, but shown is the lowest energy of all conformations assigned to the respective grid cell. The same color-scale is used for each plot of a row, and the colorbars are attached to the rightmost panel.
Mentions: The short Monte-Carlo sampling explores only a small region of conformational space around the respective starting position, which is reflected by a strong correlation between I_rms to the native complex structure before and after the Monte Carlo optimization (Figure 1A). Thus, the generated ensemble of structures is highly biased by the initial starting structures, rather than by the low-resolution energy (Figure 2C+G; Figure S4C+G in Supporting Information S1).

Bottom Line: A benchmark of 30 complexes starting from structures of the unbound binding partners shows improved performance for ReplicaDock and ZDOCK when compared to shotgun sampling at equal or less computational expense.ReplicaDock and ZDOCK consistently reach lower energies and generate significantly more near-native conformations than shotgun sampling.Additionally, the refined ReplicaDock ensembles reach significantly lower interface energies and many previously hidden features of the docking energy landscape become visible when ReplicaDock is applied.

View Article: PubMed Central - PubMed

Affiliation: Biomolecular NMR and Munich Center for Integrated Protein Science, Department Chemie, Technische Universität München, Garching, Germany.

ABSTRACT
Many protein-protein docking protocols are based on a shotgun approach, in which thousands of independent random-start trajectories minimize the rigid-body degrees of freedom. Another strategy is enumerative sampling as used in ZDOCK. Here, we introduce an alternative strategy, ReplicaDock, using a small number of long trajectories of temperature replica exchange. We compare replica exchange sampling as low-resolution stage of RosettaDock with RosettaDock's original shotgun sampling as well as with ZDOCK. A benchmark of 30 complexes starting from structures of the unbound binding partners shows improved performance for ReplicaDock and ZDOCK when compared to shotgun sampling at equal or less computational expense. ReplicaDock and ZDOCK consistently reach lower energies and generate significantly more near-native conformations than shotgun sampling. Accordingly, they both improve typical metrics of prediction quality of complex structures after refinement. Additionally, the refined ReplicaDock ensembles reach significantly lower interface energies and many previously hidden features of the docking energy landscape become visible when ReplicaDock is applied.

Show MeSH