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PPI-hotspot ID for detecting protein-protein interaction hot spots from the free protein structure.
- Source :
-
ELife [Elife] 2024 Sep 16; Vol. 13. Date of Electronic Publication: 2024 Sep 16. - Publication Year :
- 2024
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Abstract
- Experimental detection of residues critical for protein-protein interactions (PPI) is a time-consuming, costly, and labor-intensive process. Hence, high-throughput PPI-hot spot prediction methods have been developed, but they have been validated using relatively small datasets, which may compromise their predictive reliability. Here, we introduce PPI-hotspot <superscript>ID</superscript> , a novel method for identifying PPI-hot spots using the free protein structure, and validated it on the largest collection of experimentally confirmed PPI-hot spots to date. We explored the possibility of detecting PPI-hot spots using (i) FTMap in the PPI mode, which identifies hot spots on protein-protein interfaces from the free protein structure, and (ii) the interface residues predicted by AlphaFold-Multimer. PPI-hotspot <superscript>ID</superscript> yielded better performance than FTMap and SPOTONE, a webserver for predicting PPI-hot spots given the protein sequence. When combined with the AlphaFold-Multimer-predicted interface residues, PPI-hotspot <superscript>ID</superscript> yielded better performance than either method alone. Furthermore, we experimentally verified several PPI-hotspot <superscript>ID</superscript> -predicted PPI-hot spots of eukaryotic elongation factor 2. Notably, PPI-hotspot <superscript>ID</superscript> can reveal PPI-hot spots not obvious from complex structures, including those in indirect contact with binding partners. PPI-hotspot <superscript>ID</superscript> serves as a valuable tool for understanding PPI mechanisms and aiding drug design. It is available as a web server (https://ppihotspotid.limlab.dnsalias.org/) and open-source code (https://github.com/wrigjz/ppihotspotid/).<br />Competing Interests: YC, KS, YC, YH No competing interests declared, JW, CL Affiliated with Immunwork, Inc; the author has no other competing interests to declare<br /> (© 2024, Chen et al.)
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 13
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 39283314
- Full Text :
- https://doi.org/10.7554/eLife.96643