Biology subjects

Saur, M.

Publications and source records attributed to Saur, M..

4 recordsLinked to original sources

bioRxiv2026

Facilitating the identification of cryo-EM hit matter in drug discovery with Astex-Faro

Cryogenic electron microscopy (cryo-EM) is emerging as a tool for large-scale ligand screening and fragment-based drug discovery, generating extensive collections of reconstructions. At the same time, the systematic inspection of local density variations remains challenging, particularly when identifying weak or partially occupied features. Here, we present Astex-Faro, a statistical framework that defines an expected specimen state from a reference ensemble and identifies significant structural deviations in a target map through comparison against this reference. Furthermore, the method allows the enhancement of weak or poorly resolved features, enabling the recovery of signals that would otherwise be difficult to interpret. Fourier Shell Coherence (FSCoh) is introduced as a metric that quantifies consistency across reconstruction ensembles. We show that Astex-Faro reliably detects subtle structural features and improves their interpretability across datasets spanning a broad range of experimental challenges, from highly homogeneous specimens to membrane proteins, low-occupancy ligands and fragment-screening experiments. Together, these developments provide a practical framework for cryo-EM screening, increasing confidence in hit identification and reducing the risk of missed binding events.

biophysics↗

bioRxiv2025

Supervised Deep Learning for Efficient Cryo-EM Image Alignment in Drug Discovery with cryoPARES

Cryo-Electron Microscopy (cryo-EM) is a pivotal tool for determining 3D structures of biological macromolecules. Current workflows are computationally demanding and require manual intervention, creating bottlenecks for high-throughput applications like structure-based drug discovery. In such contexts, where all protein samples can be assumed to be equivalent at resolutions relevant for image alignment, information about particle poses from previous refinements could be reused. Existing methods, however, ignore this prior knowledge, aligning each dataset from scratch. We present cryoPARES, a deep learning pose estimation method trained on pre-aligned datasets. Our method not only provides accurate angular predictions significantly faster than traditional approaches but also introduces automated particle pruning capabilities that eliminate manual intervention. Together with its single-pass operation, these features enable near real-time reconstructions that provide feedback during data acquisition. We demonstrate cryoPARESs effectiveness through rapid structural determination of seven ligand-bound complexes across four distinct protein targets. We also release three fragment-bound cryo-EM datasets.

bioinformatics↗

bioRxiv2024

Arabidopsis NIM1-INTERACTING1 (NIMIN1) is a multi-domain protein controlling transition from systemic acquired resistance (SAR) to cell death

O_LINIM1-INTERACTING (NIMIN) proteins were identified by interaction with the systemic acquired resistance (SAR) key regulator NPR1. The Arabidopsis family comprises four related, yet distinct members. Ample evidence predicts that NIMIN1 is a multi-domain protein which comes into action after the onset of salicylic acid (SA) signaling prior to induction of the PR-1 defense gene. C_LIO_LIBioinformatics, protein-protein interaction assays and expression studies in tobacco were applied to explore functions of NIMIN1. C_LIO_LIThe N-terminal sequence encompassing amino acids 1 to 15 conveyed accumulation of NIMIN1 protein in planta. This newly identified segment and the known conserved NIMIN1 domains, i.e., two distinct NPR1 binding sites and an EAR motif, are neatly separated from each other by disordered regions. Co-expression of NIMIN1 and NPR1 reinforced accumulation of NPR1 protein while ectopic overexpression of NIMIN1 promoted emergence of cell death driven by the EAR motif and disturbed development of tobacco plants. C_LIO_LIWe suggest that NIMIN1 acts as a dynamic signaling agent controlling transition of pathogen-infected leaves from survival to tissue collapse. Initially, NIMIN1 binding renders the NPR1 transcription complex sensitive to the SAR signal SA enabling PR-1 transcription. At high levels of SA, NIMIN1 is outcompeted by SA from the NPR1 C-terminus, and accumulating NIMIN1 engages via its EAR motif with TOPLESS-RELATED3, thereby affecting global hormone signaling and inducing cell death in severely endangered tissue. C_LI

plant biology↗

bioRxiv2022

Differential binding of salicylic acid, phenolic acid derivatives and co- factors determines the roles of Arabidopsis NPR1 to NPR4 in plant immunity

SummaryO_LIGenetic studies have demonstrated that NPR1 is the key positive regulator of salicylic acid (SA)-induced PR-1 gene induction and systemic acquired resistance (SAR). In Arabidopsis, family members NPR1 to NPR4 share domain architecture. C_LIO_LIYeast hybrid assays were used to explore biochemical capabilities of NPR1 to NPR4. C_LIO_LIAll NPR1 to NPR4 are responsive to SA. SA perception proceeds via the conserved arginine embedded in a C-terminal LENRV-like motif. Clade 2 proteins NPR3 and NPR4 perceive SA directly, while clade 1 members NPR1 and NPR2 require interaction with partner proteins NIMIN1/NIMIN2 and TGA factors, respectively, to enable SA sensing. Intriguingly, NPR3 is considerably more sensitive to the synthetic analog 3,5-dichloroanthranilic acid than to SA, and all NPR1 to NPR4 are able to sense the microbial metabolite 6-methyl SA. C_LIO_LIWe suggest that the plant{acute}s ability to track SA and phenolic acid derivatives through NPR proteins has evolved to support diverse defense signaling outputs that are activated in parallel by agonists which may be of microbial or plant origin. In this line, NPR1-NIMIN2/NIMIN1 complex is the prime receptor for SA synthesized by plants in response to microbial attack, while NPR3 induces defense different from SAR primarily via unrecognized signal molecules. C_LI

plant biology↗