RT Journal Article
SR Electronic
T1 Novel sampling strategies and a coarse-grained score function for docking homomers, flexible heteromers, and oligosaccharides using Rosetta in CAPRI Rounds 37–45
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 749317
DO 10.1101/749317
A1 Shourya S. Roy Burman
A1 Morgan L. Nance
A1 Jeliazko R. Jeliazkov
A1 Jason W. Labonte
A1 Joseph H. Lubin
A1 Naireeta Biswas
A1 Jeffrey J. Gray
YR 2019
UL http://biorxiv.org/content/early/2019/08/30/749317.abstract
AB CAPRI Rounds 37 through 45 introduced larger complexes, new macromolecules, and multi-stage assemblies. For these rounds, we used and expanded docking methods in Rosetta to model 23 target complexes. We successfully predicted 14 target complexes and recognized and refined near-native models generated by other groups for two further targets. Notably, for targets T110 and T136, we achieved the closest prediction of any CAPRI participant. We created several innovative approaches during these rounds. Since Round 39 (target 122), we have used the new RosettaDock 4.0, which has a revamped coarse-grained energy function and the ability to perform conformer selection during docking with hundreds of pre-generated protein backbones. Ten of the complexes had some degree of symmetry in their interactions, so we tested Rosetta SymDock, realized its shortcomings, and developed the next-generation symmetric docking protocol, SymDock2, which includes docking of multiple backbones and induced-fit refinement. Since the last CAPRI assessment, we also developed methods for modeling and designing carbohydrates in Rosetta, and we used them to successfully model oligosaccharide–protein complexes in Round 41. While the results were broadly encouraging, they also highlighted the pressing need to invest in (1) flexible docking algorithms with the ability to model loop and linker motions and in (2) new sampling and scoring methods for oligosaccharide–protein interactions.