Insights into the ligand-free structure of cyclic diguanosine monophosphate I riboswitch of Vibrio cholerae using molecular dynamics simulation

Kumari, P.; Som, A.

doi:10.1101/871194

Home/Archive/bioRxiv

bioRxiv · 10.1101/871194

Insights into the ligand-free structure of cyclic diguanosine monophosphate I riboswitch of Vibrio cholerae using molecular dynamics simulation

Kumari, P.·Som, A.

View original source ↗Export metadata ↓

Abstract

Riboswitches are key cis regulatory elements present at 5 UTRs of mRNAs. They play a critical role in gene expression regulation at transcriptional and translational level by binding selectively to specific ligands followed by conformational changes. Ligands bind to the aptamer of riboswitches and their complex structures have been solved, but ligand-free riboswitches structures are not available which is important to understand specific ligand binding mechanism. In this paper, an all atom 150 nano-second (ns) molecular dynamics (MD) simulations of cyclic diguanosine monophosphate (c-di-GMP I) riboswitch aptamer domain from Vibrio cholerae were carried out to study ligand-free c-di-GMP I riboswitch aptamer structure and the binding mechanism. The Principle component analysis, cross correlation dynamics analysis and trajectory analyses revealed that the ligand-free structure has stable conformation with folded P2, P3 and an open P1 helix which opens the ligand binding helix-join-helix while the ligand-bound structure shows less deviation and remains as closed structure compared to the ligand-free structure. The junction residues significantly showed anti-correlated motions with each other elucidating the open conformation of the ligand-free aptamer of riboswitch. The identified key residues involved in binding are A18, G20, C46, A47 and C92. HighlightsO_LIThe c-di-GMP I riboswitch regulates the essential genes involved in the virulence of human bacterial pathogen V. Cholera. C_LIO_LIA 150 ns molecular dynamics run was performed to find a ligand-free stable structure of c-di-GMP I riboswitch aptamer. C_LIO_LIThe trajectory analysis resulted in stable conformation of ligand-free structure with folded P2, slightly open P3 and an unwind P1 helix. C_LIO_LIThe atomic level analyses through cross correlation dynamics and RMSF values showed the opening of catalytic pocket and unwinding P1 helix. C_LIO_LIThe identified key residues involved in binding are A18, G20, C46, A47 and C92 at the catalytic pocket. C_LI

Source connections

Published article ↗

Explore related subjects

bioinformatics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Kumari, P., Som, A.. 2019-12-11. Insights into the ligand-free structure of cyclic diguanosine monophosphate I riboswitch of Vibrio cholerae using molecular dynamics simulation. https://doi.org/10.1101/871194

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

spatialMET: an open and scalable framework for spatial metabolomics analysis

Mass spectrometry imaging (MSI) enables spatially resolved metabolomics in intact tissue sections, but analysis remains challenging at scale. Existing MSI workflows often require users to combine multiple software tools, while others rely on proprietary vendor software that limits interoperability and reproducibility. To address these challenges, we developed spatialMET, an open-source framework that provides an end-to-end workflow for MSI analysis. spatialMET provides a unified platform for preprocessing, spatial domain detection, and visualization. Downstream analyses include differential abundance testing, spatial autocorrelation and gradient analysis, dimensionality reduction, and correlation network analysis. Spatial domain detection uses hcdist, a C-based hierarchical clustering implementation that substantially reduces runtime and memory use relative to existing R-based approaches. spatialMET can be run through an interactive R Shiny application or as a standalone command-line workflow for larger datasets or high-performance computing environments. Applied to mouse small cell lung cancer MALDI-MSI data containing 284,673 pixels, spatialMET identified tumor-associated, stromal, and adjacent lung spatial domains that aligned with matched histology. Differential abundance analysis identified 117 m/z features that differed between tumor and stromal regions, while spatial autocorrelation analyses revealed spatially structured abundance patterns. Applying spatialMET to mouse lung adenocarcinoma data from an entire lung lobe containing 338,477 pixels further demonstrated scalability and captured spatial heterogeneity across tumor and surrounding lung tissue. In summary, spatialMET provides a scalable, open-source framework for end-to-end spatial metabolomics analysis, and it is distributed as a Docker container for reproducible deployment. Source code and installation instructions are available at https://github.com/biodatalab/spatialMET.

bioinformatics↗

bioRxiv2026

Probing the transcriptome response to shivering in skeletal muscle using a multilayered bioinformatics approach

Cold acclimation holds therapeutic potential for improving metabolic health. We previously demonstrated that repeated cold-induced shivering enhances insulin sensitivity in humans. However, the molecular pathways that underlie the skeletal muscle shivering response, and how these relate to beneficial physiological effects, remain poorly understood. In this study, we combined complementary bioinformatics approaches to allow in-depth analysis of the transcriptomic response of human skeletal muscle to repeated shivering. We identified a robust transcriptional signature and show a sex-specific component in the shivering skeletal muscle response, which seemed to diminish following cold adaptation. Our findings provide mechanistic insights into cold-induced muscle adaptations, shed light on potential interesting molecular targets for further investigation, and emphasize the importance of including both sexes in future cold acclimation studies.

bioinformatics↗

bioRxiv2026

An Information Geometry approach to model topological trajectories and Gene Expression Radius from UMAP geometry.

Understanding the relationship between gene expression dynamics and cellular identity remains a central challenge in single cell biology. Here, we introduce a novel computational and mathematical framework that integrates information geometry, fuzzy topology, and UMAP analysis to model gene expression landscapes derived from single cell RNA sequencing data. We formalize gene expression data as a fuzzy topological space, where interactions between expression points are governed by probabilistic distributions inspired by manifold learning approaches such as UMAP. Within this framework, we define an information geometric structure through a Fisher metric induced by these distributions, enabling the computation of geodesic trajectories that capture cellular differentiation processes. A key contribution of this work is the derivation of analytical conditions, expressed as expression radius formulas, that characterize local neighborhoods in gene expression space. These conditions allow for the identification of genes associated with stem cell states and predictions in transitional cell types in future work. Application of the proposed framework to single cell datasets reveals biologically meaningful gene sets enriched in key regulatory pathways and transcription factors, demonstrating the capacity of our approach to uncover latent structure in complex gene expression data. Our results suggest that integrating differential geometry with statistical learning theory offers a powerful paradigm for modeling genotype and phenotype relationships and cellular state transitions, with potential implications for precision medicine and systems biology.

bioinformatics↗