FREAD revisited: accurate loop structure prediction using a database search algorithm
Abstract
Loops are the most variable regions of protein structure and are, in general, the least accurately predicted. Their prediction has been approached in two ways, ab initio and database search. In recent years, it has been thought that ab initio methods are more powerful. In light of the continued rapid expansion in the number of known protein structures, we have re-evaluated FREAD, a database search method and demonstrate that the power of database search methods may have been underestimated. We found that sequence similarity as quantified by environment specific substitution scores can be used to significantly improve prediction. In fact, FREAD performs appreciably better for an identifiable subset of loops (two thirds of shorter loops and half of the longer loops tested) than the ab initio methods of MODELLER, PLOP, and RAPPER. Within this subset, FREAD's predictive ability is length independent, in general, producing results within 2A RMSD, compared to an average of over 10A for loop length 20 for any of the other tested methods. We also benchmarked the prediction protocols on a set of 212 loops from the model structures in CASP 7 and 8. An extended version of FREAD is able to make predictions for 127 of these, it gives the best prediction of the methods tested in 61 of these cases. In examining FREAD's ability to predict in the model environment, we found that whole structure quality did not affect the quality of loop predictions.
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Antibody-specific knowledge-based approaches are fast and accurate if a template is available.
“Antibody-specific knowledge-based approaches are fast and accurate if a template is available [103].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [103]
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- Authors
- Choi, Y., & Deane, C. M.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Choi, Yoonjoo
- Venue
- Proteins Structure Function and Bioinformatics
- Publisher
- Wiley
- Published
- 2009-12-23
- Volume
- 78
- Issue
- 6
- Pages
- 1431-1440
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- OpenAlex
- W2005140643
- Cited by
- 161
- References
- 48
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 10 · 2022: 7 · 2021: 17 · 2020: 12 · 2019: 17 · 2018: 11 · 2017: 12 · 2016: 8 · 2015: 11 · 2014: 11 · 2013: 16 · 2012: 10
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Oxford
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Keywords
- database searching, sequence similarity, MODELLER, loop length, structural quality
- MeSH terms
- Algorithms, Models, Molecular, Proteins, Protein Structure, Secondary, Computational Biology, Databases, Protein
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