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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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Small angle X‐ray scattering‐assisted protein structure prediction in CASP13 and emergence of solution structure differences
Abstract Small angle X‐ray scattering (SAXS) measures comprehensive distance information on a protein's structure, which can constrain and guide computational structure prediction algorithms. Here, we evaluate structure predictions of 11 monomeric and oligomeric proteins for which SAXS data were collected and provided to predictors in the 13th round of the Critical Assessment of protein Structure Prediction (CASP13). The category for SAXS‐assisted predictions made gains in certain areas for CASP13 compared to CASP12. Improvements included higher quality data with size exclusion chromatography‐SAXS (SEC‐SAXS) and better selection of targets and communication of results by CASP organizers. In several cases, we can track improvements in model accuracy with use of SAXS data. For hard multimeric targets where regular folding algorithms were unsuccessful, SAXS data helped predictors to build models better resembling the global shape of the target. For most models, however, no significant improvement in model accuracy at the domain level was registered from use of SAXS data, when rigorously comparing SAXS‐assisted models to the best regular server predictions. To promote future progress in this category, we identify successes, challenges, and opportunities for improved strategies in prediction, assessment, and communication of SAXS data to predictors. An important observation is that, for many targets, SAXS data were inconsistent with crystal structures, suggesting that these proteins adopt different conformation(s) in solution. This CASP13 result, if representative of PDB structures and future CASP targets, may have substantive implications for the structure training databases used for machine learning, CASP, and use of prediction models for biology.
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- Award ID(s):
- 1832184
- PAR ID:
- 10459443
- 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. 1298-1314
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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