10779/crick.12707894.v1
Mieczyslaw Torchala
Mieczyslaw
Torchala
Tereza Gerguri
Tereza
Gerguri
Raphael AG Chaleil
Raphael AG
Chaleil
Patrick Gordon
Patrick
Gordon
Francis Russell
Francis
Russell
Miriam Keshani
Miriam
Keshani
Paul A Bates
Paul A
Bates
Enhanced sampling of protein conformational states for dynamic cross-docking within the protein-protein docking server SwarmDock.
The Francis Crick Institute
2020
Aether Engine
CAPRI
DFIRE2
SwarmDock
conformational selection
conformational states space sampling
crossdocking
induced fit
normal modes
protein-protein docking
protein-protein interactions
cross-docking
Bates FC001003
Bioinformatics
06 Biological Sciences
08 Information and Computing Sciences
01 Mathematical Sciences
2020-07-24 13:02:35
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Enhanced_sampling_of_protein_conformational_states_for_dynamic_cross-docking_within_the_protein-protein_docking_server_SwarmDock_/12707894
The formation of specific protein-protein interactions is often key to a protein's function. During complex formation, each protein component will undergo a change of conformational state, for some these changes are relatively small and reside primarily at the sidechain level; however, others may display notable backbone adjustments. One of the classic problems in the protein docking field is to be able to a priori predict the extent of such conformational changes. In this work, we investigated three protocols to find the most suitable input structure conformations for cross-docking, including a robust sampling approach in normal mode space. Counterintuitively, knowledge of the theoretically best combination of normal modes for unbound-bound transition doesn't always lead to the best results. We used a novel spatial partitioning library, Aether Engine (see Supplementary Materials), to efficiently search the conformational states of 56 receptor/ligand pairs, including a recent CAPRI target, in a systematic manner and selected diverse conformations as input to our automated docking server, SwarmDock; a server that allows moderate conformational adjustments during the docking process. In essence, here we present a dynamic cross-docking protocol, which when benchmarked against the simple simpler approach of just docking the unbound components, shows a 10% uplift in quality of the top docking pose. This article is protected by copyright. All rights reserved.