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Abstract Targets in the protein docking experiment CAPRI (Critical Assessment of Predicted Interactions) generally present new challenges and contribute to new developments in methodology. In rounds 38 to 45 of CAPRI, most targets could be effectively predicted using template‐based methods. However, the server ClusPro required structures rather than sequences as input, and hence we had to generate and dock homology models. The available templates also provided distance restraints that were directly used as input to the server. We show here that such an approach has some advantages. Free docking with template‐based restraints using ClusPro reproduced some interfaces suggested by weak or ambiguous templates while not reproducing others, resulting in correct server predicted models. More recently we developed the fully automated ClusPro TBM server that performs template‐based modeling and thus can use sequences rather than structures of component proteins as input. The performance of the server, freely available for noncommercial use athttps://tbm.cluspro.org, is demonstrated by predicting the protein‐protein targets of rounds 38 to 45 of CAPRI.
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Template‐based modeling by ClusPro in CASP13 and the potential for using co‐evolutionary information in docking
Abstract As a participant in the joint CASP13‐CAPRI46 assessment, the ClusPro server debuted its new template‐based modeling functionality. The addition of this feature, called ClusPro TBM, was motivated by the previous CASP‐CAPRI assessments and by the proven ability of template‐based methods to produce higher‐quality models, provided templates are available. In prior assessments, ClusPro submissions consisted of models that were produced via free docking of pre‐generated homology models. This method was successful in terms of the number of acceptable predictions across targets; however, analysis of results showed that purely template‐based methods produced a substantially higher number of medium‐quality models for targets for which there were good templates available. The addition of template‐based modeling has expanded ClusPro's ability to produce higher accuracy predictions, primarily for homomeric but also for some heteromeric targets. Here we review the newest additions to the ClusPro web server and discuss examples of CASP‐CAPRI targets that continue to drive further development. We also describe ongoing work not yet implemented in the server. This includes the development of methods to improve template‐based models and the use of co‐evolutionary information for data‐assisted free docking.
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- PAR ID:
- 10459414
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Proteins: Structure, Function, and Bioinformatics
- Volume:
- 87
- Issue:
- 12
- ISSN:
- 0887-3585
- Page Range / eLocation ID:
- p. 1241-1248
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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