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Updated: Aug 6, 2026
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Navigating the Mass Spectrometry-Based Proteomic Data Using Free Computational Tools
Published on: August 19, 2025
Pan-Cancer Landscape of Spatial PTM and Mutation Clusters Reveals Allosteric Regulation of Protein-Protein
Dongfang Luo1, Jiani Zheng1, Xikun Du1
1Biomedical Basic Research Center (BBRC) of Jiangsu, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou215123, Jiangsu, China.
Journal of Chemical Information and Modeling
|July 17, 2026
Summary
We developed ClusTar to map clusters of post-translational modifications (PTMs) and mutations in protein interactions across cancers. These clusters act as allosteric hotspots, offering new therapeutic targets for cancer.
Area of Science:
- Cancer Biology
- Structural Biology
- Bioinformatics
Background:
- Post-translational modifications (PTMs) and somatic mutations are common in cancer.
- Their spatial organization and regulation within protein-protein interactions (PPIs) are not well understood.
Purpose of the Study:
- To develop a structural framework (ClusTar) for identifying PTM-mutation clusters within PPIs.
- To link these clusters to protein dynamics and functional regulation in cancer.
Main Methods:
- Integrated TCGA genomics, CPTAC proteomics, and PPI structural data.
- Applied ClusTar to identify and analyze PTM-mutation clusters across ten cancer types.
- Investigated cluster-mediated protein dynamics and allosteric communication.
Main Results:
- Identified 3,966 high-confidence PTM-mutation clusters enriched in functional residues and ligand-binding pockets.
- Found clusters are mechanically coupled to PPI interfaces, mediating long-range allosteric effects.
- Observed specific mutations in RhoA complexes rewire allosteric pathways and enhance cell migration.
Conclusions:
- Established a pan-cancer structural atlas of PTM-mutation clusters.
- Highlighted allosteric hotspots as potential targets for modulating PPIs in cancer therapy.
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