Assessing the binding properties of CASP14 targets and models
Open accessAbstract
An important question is how well the models submitted to CASP retain the properties of target structures. We investigate several properties related to binding. First we explore the binding of small molecules as probes, and count the number of interactions between each residue and such probes, resulting in a binding fingerprint. The similarity between two fingerprints, one for the X‐ray structure and the other for a model, is determined by calculating their correlation coefficient. The fingerprint similarity weakly correlates with global measures of accuracy, and GDT_TS higher than 80 is a necessary but not sufficient condition for the conservation of surface binding properties. The advantage of this approach is that it can be carried out without information on potential ligands and their binding sites. The latter information was available for a few targets, and we explored whether the CASP14 models can be used to predict binding sites and to dock small ligands. Finally, we tested the ability of models to reproduce protein–protein interactions by docking both the X‐ray structures and the models to their interaction partners in complexes. The analysis showed that in CASP14 the quality of individual domain models is approaching that offered by X‐ray crystallography, and hence such models can be successfully used for the identification of binding and regulatory sites, as well as for assembling obligatory protein–protein complexes. Success of ligand docking, however, often depends on fine details of the binding interface, and thus may require accounting for conformational changes by simulation methods.
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Analysis by the function assessors shows that simply using more accurate models of the constituent proteins will have a major impact on the effectiveness of classical docking methods.
“First, analysis by the function assessors8 shows that simply using more accurate models of the constituent proteins will have a major impact on the effectiveness of classical docking methods.”
From Critical assessment of methods of protein structure prediction (CASP)—Round <scp>XIV</scp> (2021) · cites this paper as [8]
The CASP function assessors have shown that improved accuracy of structure models will improve the performance of current ligand docking methods.
“As with protein docking, the CASP function assessors have shown that improved accuracy of structure models will improve the performance of current ligand docking methods8, with implications for screening ligand specificity across all proteins.”
From Critical assessment of methods of protein structure prediction (CASP)—Round <scp>XIV</scp> (2021) · cites this paper as [8]
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- Authors
- Egbert, M., Ghani, U., Ashizawa, R., Kotelnikov, S., Nguyen, T., Desta, I., Hashemi, N., Padhorny, D., Kozakov, D., & Vajda, S.
- Affiliations
- Boston University (US)
- Stony Brook University (US)
- Department of Biomedical Engineering Boston University Boston Massachusetts USA
- Corresponding author
- Padhorny, Dzmitry
- Kozakov, Dima
- ORCID
- Venue
- Proteins: Structure, Function, and Bioinformatics
- Publisher
- Wiley
- Published
- 2021-08-19
- Volume
- 89
- Issue
- 12
- Pages
- 1922-1939
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- PMC
- PMC8616776
- OpenAlex
- W3188448537
- Cited by
- 10
- References
- 43
- Citations by year
- 2023: 2 · 2022: 4 · 2021: 4
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R21GM127952, R35GM118078, RM1135136)
- National Science Foundation (AF 1645512, DBI 1759277)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- CASP14, protein structure prediction, model accuracy assessment, small molecule binding, protein-ligand docking, binding site prediction, protein-protein interaction, GDT_TS, conformational change
- MeSH terms
- Binding Sites, Ligands, Models, Molecular, Protein Binding, Protein Conformation, Proteins, Software, Computational Biology, Protein Interaction Domains and Motifs, Molecular Docking Simulation
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