Biology subjects

Lu, X.-J.

Publications and source records attributed to Lu, X.-J..

3 recordsLinked to original sources

bioRxiv2026

Structural Pockets and Interacting RNA-Associated Ligands (SPIRAL): A DSSR-enabled Meta-Analysis of RNA-Small Molecule Recognition

Small molecules that target structured RNA hold therapeutic promise across a wide range of diseases, yet the structural principles governing RNA-ligand recognition remain poorly defined. We present SPIRAL (Structural Pockets and Interacting RNA-Associated Ligands), a curated database of 1,098 RNA-small molecule structures from the Protein Data Bank covering 1,137 ligand-binding events across six functional RNA categories. A customized pipeline built on DSSR (Dissecting the Spatial Structure of RNA) extracts structural interaction parameters from each complex, capturing stacking geometry, hydrogen-bond topology resolved by RNA moiety, groove engagement, and tertiary motif context. Unsupervised clustering of these fingerprints resolves six mechanistically distinct binding modes, the distribution of which is strongly governed by RNA functional class. To enable category-independent comparison of interaction quality across these diverse modes, we introduce the Composite Binding Quality Score (CBQS), a seven-metric framework that ranks riboswitches highest and regulatory RNA motifs lowest among the six categories. Across 275 affinity-characterized entries, C2'-endo sugar pucker count and total buried contact surface area emerge as the dominant predictors of binding affinity, converging with the structural features most underengaged by current regulatory RNA motif binders. SPIRAL provides a data-driven foundation for the rational design of next-generation RNA-targeted therapeutics.

bioinformatics↗

bioRxiv2022

Structure-based prediction and characterization of photo-crosslinking in native protein-RNA complexes

UV-crosslinking of protein and RNA in direct contacts has been widely used to study protein-RNA complexes despite our poor understanding on the mechanisms of photo-crosslinking. This knowledge gap is due to the challenge to precisely map the crosslink sites in protein and RNA simultaneously in their native sequence and structural contexts. Here we developed PxR3D-map, a computational method to analyze protein-RNA interactions and photo-crosslinking by bridging crosslinked nucleotides and amino acids mapped using different assays with protein-RNA complex structures. PxR3D-map reliably predicts crosslink sites using structural information characterizing protein-RNA interaction interfaces. We found that photo-crosslinking is facilitated by base stacking with not only aromatic residues, but also dipeptide bonds that involve glycine, and distinct mechanisms are utilized by different types of RNA-binding domains. Our work suggests protein-RNA photocrosslinking is highly selective in the cellular environment, which can guide interpretation of data generated by UV-crosslinking-based assays and further technology development.

biophysics↗

bioRxiv2018

Simulations and Electrostatic Analysis Suggest an Active Role for DNA Conformational Changes During Genome Packaging by Bacteriophages

Motors that move DNA, or that move along DNA, play essential roles in DNA replication, transcription, recombination, and chromosome segregation. The mechanisms by which these DNA translocases operate remain largely unknown. Some double-stranded DNA (dsDNA) viruses use an ATP-dependent motor to drive DNA into preformed capsids. These include several human pathogens, as well as dsDNA bacteriophages - viruses that infect bacteria. We previously proposed that DNA is not a passive substrate of bacteriophage packaging motors but is, instead, an active component of the machinery. Computational studies on dsDNA in the channel of viral portal proteins reported here reveal DNA conformational changes consistent with that hypothesis. dsDNA becomes longer (\"stretched\") in regions of high negative electrostatic potential, and shorter (\"scrunched\") in regions of high positive potential. These results suggest a mechanism that couples the energy released by ATP hydrolysis to DNA translocation: The chemical cycle of ATP binding, hydrolysis and product release drives a cycle of protein conformational changes. This produces changes in the electrostatic potential in the channel through the portal, and these drive cyclic changes in the length of dsDNA. The DNA motions are captured by a coordinated protein-DNA grip-and-release cycle to produce DNA translocation. In short, the ATPase, portal and dsDNA work synergistically to promote genome packaging.

biophysics↗