Systematic Analysis of Helical Protein Interfaces Reveals Targets for Synthetic Inhibitors
By Andrea L. Jochim, Paramjit S. Arora. 2010
162 citations recorded by the source corpus.
Synthetic inhibitors of protein-protein interactions are being discovered despite the inherent challenge in targeting large contact surfaces with small molecules. An analysis of available examples identifies common features of complexes that make them tractable for small molecules. We deduced that relative disposition and energetic contributions of “hot spot” residues provide a predictive scale for the potential of protein-protein interactions to be inhibited by small molecules. Based on this model, we analyzed the full set of helical protein interfaces in the Protein Data Bank to identify those that are potentially suitable candidates for synthetic ligands.
Subfields: Computational Theory and Mathematics, Materials Chemistry, Molecular Biology
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In Computational Theory and Mathematics
- David Baker
- Jeffrey J. Gray
- Rhiju Das
- Sergey Lyskov
- Jens Meiler
- John Karanicolas
- Ragul Gowthaman
- Tanja Kortemme
In Materials Chemistry
- David Baker
- Jeffrey J. Gray
- Tanja Kortemme
- Frank DiMaio
- Jens Meiler
- Hahnbeom Park
- Xingjie Pan
- Santrupti Nerli
In Molecular Biology
- David Baker
- Jeffrey J. Gray
- Tanja Kortemme
- Xingjie Pan
- Jens Meiler
- Frank DiMaio
- Rhiju Das
- Brian D. Weitzner
Citations in the corpus
- Macromolecular modeling and design in Rosetta: recent methods and frameworks (2020, background): “Many protein-protein interactions (PPI) are mediated by often disordered peptide segments that are responsible for most of the binding energy 112,211 – 213 .”
- Comprehensive Analysis of Loops at Protein-Protein Interfaces for Macrocycle Design (2014, unknown): “10,11 In addition, an algorithm called PeptiDerive was used to search a set of 151 pre-selected PPIs for short segments that contain multiple hot spots, regardless of structure.”