Limits...
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.

Show MeSH
Electrostatic surface potential of native (A–D) and interchain_cen preferred conformation (E–H) in all-atom representation.A) native complex with receptor in green and ligand in red B) electrostatics map of the native complex C) electrostatics map of native ligand interface D) electrostatics map of native receptor interface E) interchain_cen preferred conformation after refinement F) electrostatics map G) electrostatics map of receptor interface H) electrostatics map of ligand interface. The yellow lines in C, D, G and H indicate the respective interface regions, and number pairs (e.g. 1 in C and 1′ in D) indicate corresponding contact regions. Relations of viewing angle are given between panels where required.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3756964&req=5

pone-0072096-g008: Electrostatic surface potential of native (A–D) and interchain_cen preferred conformation (E–H) in all-atom representation.A) native complex with receptor in green and ligand in red B) electrostatics map of the native complex C) electrostatics map of native ligand interface D) electrostatics map of native receptor interface E) interchain_cen preferred conformation after refinement F) electrostatics map G) electrostatics map of receptor interface H) electrostatics map of ligand interface. The yellow lines in C, D, G and H indicate the respective interface regions, and number pairs (e.g. 1 in C and 1′ in D) indicate corresponding contact regions. Relations of viewing angle are given between panels where required.

Mentions: A–B) shotgun and ReplicaDock sample the low-resolution docking stage with ‘capped’ centroid energy function. C–D) shotgun and ReplicaDock sample the low-resolution docking stage with centroid energy function with no cap. The structure indicated by the red circle will be shown in Figure 8.


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

Zhang Z, Lange OF - PLoS ONE (2013)

Electrostatic surface potential of native (A–D) and interchain_cen preferred conformation (E–H) in all-atom representation.A) native complex with receptor in green and ligand in red B) electrostatics map of the native complex C) electrostatics map of native ligand interface D) electrostatics map of native receptor interface E) interchain_cen preferred conformation after refinement F) electrostatics map G) electrostatics map of receptor interface H) electrostatics map of ligand interface. The yellow lines in C, D, G and H indicate the respective interface regions, and number pairs (e.g. 1 in C and 1′ in D) indicate corresponding contact regions. Relations of viewing angle are given between panels where required.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756964&req=5

pone-0072096-g008: Electrostatic surface potential of native (A–D) and interchain_cen preferred conformation (E–H) in all-atom representation.A) native complex with receptor in green and ligand in red B) electrostatics map of the native complex C) electrostatics map of native ligand interface D) electrostatics map of native receptor interface E) interchain_cen preferred conformation after refinement F) electrostatics map G) electrostatics map of receptor interface H) electrostatics map of ligand interface. The yellow lines in C, D, G and H indicate the respective interface regions, and number pairs (e.g. 1 in C and 1′ in D) indicate corresponding contact regions. Relations of viewing angle are given between panels where required.
Mentions: A–B) shotgun and ReplicaDock sample the low-resolution docking stage with ‘capped’ centroid energy function. C–D) shotgun and ReplicaDock sample the low-resolution docking stage with centroid energy function with no cap. The structure indicated by the red circle will be shown in Figure 8.

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