TY - JOUR
T1 - Novel sampling strategies and a coarse-grained score function for docking homomers, flexible heteromers, and oligosaccharides using Rosetta in CAPRI rounds 37–45
AU - Roy Burman, Shourya S.
AU - Nance, Morgan L.
AU - Jeliazkov, Jeliazko R.
AU - Labonte, Jason W.
AU - Lubin, Joseph H.
AU - Biswas, Naireeta
AU - Gray, Jeffrey J.
N1 - Funding Information:
This work has been supported by grants from the National Institutes of Health, USA, namely, grants R01-GM078221 (JJG, SSRB, MLN, JRJ, JWL), T32-GM008403 (MLN, JRJ), F32-CA189246 (JWL) and F31-GM123616 (JRJ), and the National Science Foundation, USA award 1507736. Computations in this study have been performed in part on the Maryland Advanced Research Computing Center (MARCC) Blue Crab cluster. The authors thank Prof. Jamie Spangler of Johns Hopkins University for her advice on target 122.
Funding Information:
This work has been supported by grants from the National Institutes of Health, USA, namely, grants R01‐GM078221 (JJG, SSRB, MLN, JRJ, JWL), T32‐GM008403 (MLN, JRJ), F32‐CA189246 (JWL) and F31‐GM123616 (JRJ), and the National Science Foundation, USA award 1507736. Computations in this study have been performed in part on the Maryland Advanced Research Computing Center (MARCC) Blue Crab cluster. The authors thank Prof. Jamie Spangler of Johns Hopkins University for her advice on target 122.
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Critical Assessment of PRediction of Interactions (CAPRI) rounds 37 through 45 introduced larger complexes, new macromolecules, and multistage 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 pregenerated 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. Although the results were broadly encouraging, they also highlighted the pressing need to invest in (a) flexible docking algorithms with the ability to model loop and linker motions and in (b) new sampling and scoring methods for oligosaccharide-protein interactions.
AB - Critical Assessment of PRediction of Interactions (CAPRI) rounds 37 through 45 introduced larger complexes, new macromolecules, and multistage 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 pregenerated 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. Although the results were broadly encouraging, they also highlighted the pressing need to invest in (a) flexible docking algorithms with the ability to model loop and linker motions and in (b) new sampling and scoring methods for oligosaccharide-protein interactions.
KW - CAPRI
KW - Rosetta
KW - conformational change
KW - protein docking
KW - protein-oligosaccharide interaction
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U2 - 10.1002/prot.25855
DO - 10.1002/prot.25855
M3 - Article
C2 - 31742764
AN - SCOPUS:85076104130
SN - 0887-3585
VL - 88
SP - 973
EP - 985
JO - Proteins: Structure, Function and Bioinformatics
JF - Proteins: Structure, Function and Bioinformatics
IS - 8
ER -