Dr. Lim, Carmay 's orcid link picture Dr. Lim, Carmay 's publons link picture

Dr. Lim, Carmay

Emeritus Research Fellow
  • +886-2-2789-9043 (Lab) (Room No: N117)
  • +886-2-2652-3031 (Office)
  • +886-2-2788-7641 (Fax)

Specialty:
  • Computational Biophysics
  • Computational Chemistry
  • Bioinformatics

Education and Positions:
  • 1984, Ph.D. in Chemical Physics, University of Minnesota, Minneapolis

    1979, B.S. in Chemistry, Royal Holloway College, London University

     


Highlight Detail
...

PPI-hotspotID for detecting protein-protein interaction hot spots from the free protein structure

Dr. Lim, Carmay
eLife, Sep 16, 2024

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-hotspotID, 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-hotspotID 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-hotspotID yielded better performance than either method alone. Furthermore, we experimentally verified several PPI-hotspotID-predicted PPI-hot spots of eukaryotic elongation factor 2. Notably, PPI-hotspotID can reveal PPI-hot spots not obvious from complex structures, including those in indirect contact with binding partners. PPI-hotspotID 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/).