Sabapathy, T. | Search bioRxiv

bioRxiv2026

DPI-score: A deep learning-based metric for assessing protein-protein interfaces in cryo-EM derived assemblies

Advances in cryoEM have led to a surge in high-resolution structures; however, model building and refinement at resolutions (>=3 [A]) and in regions with variable local resolution remain challenging, making validation essential. CryoEM derived assemblies often contain extensive protein-protein interfaces, however, most existing validation metrics focus on density fit or overall geometry without directly assessing interface quality. To address this, we present DPI-Score, a deep learning-based metric for assessing protein-protein interfaces in cryoEM derived complexes. The method uses only raw structural coordinates of interface atoms, without requiring engineered features, and achieves 87.53% validation accuracy. DPI-Score was applied to 29,120 interfaces from 6,011 fitted entries with resolutions worse than 3 [A] in the Electron Microscopy Data Bank. Here, we show that DPI-Score provides complementary information to existing validation metrics and can identify interface errors in modelled assemblies that are not detected by density-based scores alone.

bioinformatics↗

bioRxiv2025

Enterocloster citroniae and related gut microbiome species modulate Vibrio cholerae biofilm formation through the production of bioactive small molecules

Cholera is a diarrheal disease that affects millions of people globally. Although the causative agent, Vibrio cholerae, has been extensively studied in isolation, investigation of its interactions with the gut microbiota started relatively recently. We and others previously showed that microbiota-derived metabolites significantly influence V. cholerae behavior. By investigating how an organic extract of human feces affects V. cholerae gene expression, we showed that gut metabolites strongly suppress swimming motility, a trait important for host colonization. Interestingly, extracts of pure cultures of a gut commensal, Enterocloster citroniae, recapitulated this inhibition. Here, we present a comprehensive examination of the effect of small molecules produced by E. citroniae and related species on V. cholerae behavior. We show that E. citroniae small molecules inhibit motility by various V. cholerae strains, and that several phylogenetically related species produce this activity, although the magnitude of the effect varies between strains. Using biofilm formation assays in static and flow conditions, we show that V. cholerae strongly induces biofilm formation in response to E. citroniae metabolites. Transcriptome and reporter analyses showed that several genes involved in synthesis of an extracellular polysaccharide are induced by E. citroniae metabolites. Lastly, we show that V. cholerae interactions with host cells are also modulated by this commensal. These findings advance our understanding of microbiome-pathogen interactions and how commensal bacteria influence V. cholerae virulence through the production of small molecules. In the future, this knowledge may be used to design novel microbiome-based therapeutic approaches to combat cholera and other infections. ImportanceThe human gut is home to a dense and rich community of microbes termed microbiota. This community has critical functions for host health, including protection against enteric pathogens. Despite this important role, we have only recently scratched the surface of the interactions that occur between members of the microbiota and pathogenic invaders. Cholerae is a disease that still causes significant morbidity and mortality worldwide. Studying how the causative agent, Vibrio cholerae, interacts with the microbiota will have implications not only for our understanding of this important microbial community, but may also lead to the development of new therapeutic strategies against cholera and potentially other infectious diseases.

microbiology↗