TY - JOUR
T1 - Small angle X-ray scattering-assisted protein structure prediction in CASP13 and emergence of solution structure differences
AU - Hura, Greg L.
AU - Hodge, Curtis D.
AU - Rosenberg, Daniel
AU - Guzenko, Dmytro
AU - Duarte, Jose M.
AU - Monastyrskyy, Bohdan
AU - Grudinin, Sergei
AU - Kryshtafovych, Andriy
AU - Tainer, John A.
AU - Fidelis, Krzysztof
AU - Tsutakawa, Susan E.
N1 - Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - SAS
KW - SAXS
KW - complexes
KW - disorder
KW - experimental restraints
KW - flexibility
KW - modeling
KW - solution scattering
KW - structure prediction
KW - unstructured regions
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U2 - 10.1002/prot.25827
DO - 10.1002/prot.25827
M3 - Article
C2 - 31589784
AN - SCOPUS:85071243487
SN - 0887-3585
VL - 87
SP - 1298
EP - 1314
JO - Proteins: Structure, Function and Bioinformatics
JF - Proteins: Structure, Function and Bioinformatics
IS - 12
ER -