Utilizing small molecules to probe and harness the proteome by pooled protein tagging with ligandable domains by Katherine E. Larrimore, Yevgeniy V. Serebrenik

“…We also discuss potential applications in drug discovery such as high-throughput screening for therapeutic targets with insights for bifunctional ligand optimization. By integrating pooled protein tagging with ligand-binding domains and chemical probes, we highlight how the fusion of chemical biology and functional genomics is paving the way for innovative research avenues and transformative advances in cell biology and pharmacology.…”
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Functional dissection of the TBK1 molecular network. by Adriana Goncalves, Tilmann Bürckstümmer, Evelyn Dixit, Ruth Scheicher, Maria W Górna, Evren Karayel, Cristina Sugar, Alexey Stukalov, Tiina Berg, Robert Kralovics, Melanie Planyavsky, Keiryn L Bennett, Jacques Colinge, Giulio Superti-Furga

“…TANK-binding kinase 1 (TBK1) and inducible IκB-kinase (IKK-i) are central regulators of type-I interferon induction. …”
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Parental Phasing Study Identified Lineage-Specific Variants Associated with Gene Expression and Epigenetic Modifications in European–Chinese Hybrid Pigs by Chenyu Li, Mei Ge, Keren Long, Ziyin Han, Jing Li, Mingzhou Li, Zhiyan Zhang

“…Understanding how hybrids integrate lineage-specific regulatory variants at the haplotype level is crucial for elucidating the genetic basis of heterosis in livestock. …”
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Structure-based network analysis of activation mechanisms in the ErbB family of receptor tyrosine kinases: the regulatory spine residues are global mediators of structural stabilit... by Kevin A James, Gennady M Verkhivker

“…We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. …”
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Target screening and optimization of candidate compounds for breast cancer treatment using bioinformatics and computational chemistry approaches by Jian Xu, Xue Li, Yiduo Jia, Yiduo Jia

“…A pharmacophore model was constructed based on binding information to guide the virtual screening of additional compounds with activity. …”
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Linking machine learning and biophysical structural features in drug discovery by Armin Ahmadi, Shivangi Gupta, Vineetha Menon, Jerome Baudry

“…By leveraging pharmacophore descriptors, the AI/ML framework prioritized features uniquely associated with ligand-selected conformations, enabling a mechanism-driven understanding of binding interactions. This novel approach integrates biophysical insights with machine learning, focusing on pharmacophoric properties such as charge, hydrogen bonding, hydrophobicity, and aromaticity.ResultsResults showed significant enrichment of true positive ligands—improving database enrichment by up to 54-fold compared to random selection—demonstrating the robustness of this approach across diverse proteins.ConclusionUnlike conventional structure-based or ligand-based screening methods, this work emphasizes the role of specific protein conformations in driving ligand binding, making the process highly interpretable and actionable for drug discovery. …”
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Examining peptide–gold nanoparticle interactions through explainable machine learning by Malak Gamal Abdelmeguid, Jose Isagani B. Janairo, Nishanth G. Chemmangattuvalappil

“…The model was trained and evaluated on a dataset composed of 1720 peptides and their experimentally determined binding affinity for gold nanoparticles. The created model demonstrates reliable accuracy in distinguishing strong-binding peptides from weak binders. …”
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A carboxy-terminal trimerization domain stabilizes conformational epitopes on the stalk domain of soluble recombinant hemagglutinin substrates. by Florian Krammer, Irina Margine, Gene S Tan, Natalie Pica, Jens C Krause, Peter Palese

“…Since most of these antibodies bind to conformational epitopes, the structural integrity of hemagglutinin substrates for the detection and quantification of these antibodies is of high importance. …”
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Discovery of novel DdlA inhibitors in multidrug-resistant Pseudomonas aeruginosa using virtual screening, molecular docking, and dynamics simulations by Fahad M. Aldakheel, Shatha A. Alduraywish

“…This study utilized in silico computational approaches to identify the novel inhibitors for d-alanine–d-alanine ligase A (DdlA), an essential enzyme for the bacterial peptidoglycan biosynthesis pathway necessary for cell wall integrity. A structure-based virtual screening of The Medicinal Fungi Secondary Metabolites and Therapeutics (MeFSAT) chemical library was conducted, followed by molecular docking to evaluate the binding affinity of small molecules to the DdlA active site. …”
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Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53. by Kristina Kirschner, Shamith A Samarajiwa, Jonathan M Cairns, Suraj Menon, Pedro A Pérez-Mancera, Kosuke Tomimatsu, Camino Bermejo-Rodriguez, Yoko Ito, Tamir Chandra, Masako Narita, Scott K Lyons, Andy G Lynch, Hiroshi Kimura, Tetsuya Ohbayashi, Simon Tavaré, Masashi Narita

“…The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. …”
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MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain. by Sabine Lagger, John C Connelly, Gabriele Schweikert, Shaun Webb, Jim Selfridge, Bernard H Ramsahoye, Miao Yu, Chuan He, Guido Sanguinetti, Lawrence C Sowers, Malcolm D Walkinshaw, Adrian Bird

“…Mutations in the gene encoding the methyl-CG binding protein MeCP2 cause several neurological disorders including Rett syndrome. …”
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Computational advances in the design and discovery of artemis inhibitors for radiosensitization in cancer therapy by Maryam Bashir, Usman Abdullah, Sadia Nazir, Farhan Siddique, Nasir Jalal

“…Among the top hits, compound 42 showed a highly stable binding profile, with a favorable MMGBSA binding energy of −36.94 kcal/mol. …”
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Function of HP1BP3 as a linker histone is regulated by linker histone chaperones, NPM1 and TAF-I by Miharu Hisaoka, Tetsuro Komatsu, Takuma Hashimoto, Jianhuang Lin, Yasuyuki Ohkawa, Mitsuru Okuwaki

“…Abstract Background Linker histones constitute a class of proteins that are responsible for the formation of higher-order chromatin structures. Core histones are integral components of nucleosome core particles (NCPs), whereas linker histones bind to linker DNA between NCPs. …”
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IGF2BP3 prefers to regulate alternative splicing of genes associated with the progression of gastric cancer in AGS cells by Xiangyue Zeng, Yu Zhang, Tiannake Shapaer, Abulajiang Abudoukelimu, Zeliang Zhao, Binlin Ma

“…More importantly, IGF2BP3-OE significantly modulated AS pattern of thousands of genes, which were enriched in mRNA splicing, cell proliferation, and translation pathways. By integrating the RNA binding profile of IGF2BP3, we found IGF2BP3 binding preferred to modulate the splicing pattern of bound genes, and the overlapped genes were also enriched in mRNA splicing pathways. …”
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ImmuProgML: machine learning-based dissection of cancer-immune dynamics during tumor progression to improve immunotherapy by Hanxiao Zhou, Lan Mei, Qianyi Lu, Yakun Zhang, Yue Sun, Caiyu Zhang, Han Jiang, Jiajun Zhou, Xia Li, Yunpeng Zhang, Shangwei Ning

“…While immunotherapy has significantly improved outcomes, current biomarker models lack integration of cancer-immune interactions and progression dynamics. …”
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The NR_109/FUBP1/c-Myc axis regulates TAM polarization and remodels the tumor microenvironment to promote cancer development by Baoen Shan, Cong Zhang, Guogui Sun, Hongtao Zhang, Xiaoya Li, Sisi Wei, Suli Dai, Huixia Wang, Lianmei Zhao

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Deciphering the angiogenic potential of Zhishi Xiebai Guizhi decoction in coronary heart disease: an in-depth network pharmacology and experimental investigation by Yingli Mo, Yuping Xu, Bei Lu, Xiaojuan Fan, Qingshuang Zhang, Shaowu Cheng, Qinghua Peng

“…Abstract ZXGD Decoction, a traditional Chinese formulation historically used for cardiovascular ailments, was evaluated for its efficacy in coronary heart disease (CHD) through an integrated network pharmacology and randomized controlled trial (RCT) approach. …”
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Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications by Trang Thao Quoc Pham, Yung-Che Kuo, Wei-Ling Chang, Hao-Jui Weng, Yen-Hua Huang

“…The dual roles of key components of the adhesive niche, including the dermo-epidermal junction and adherens junction, various cell types—especially immune cells and fibroblasts—as well as major signaling pathways such as Sonic hedgehog (Shh), Wingless-related integration site (Wnt)/β-catenin, YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif), and Notch, are highlighted. …”
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Surface‐Engineered Cenospheres Encapsulating Phase Change Materials for Functional Cementitious Composites by Sahand Rahemipoor, Carsten Kuenzel, Toms Valdemārs Eiduks, Andrei Shishkin, Mohammadreza Izadifar, Neven Ukrainczyk, Eduardus Koenders, Navid Ranjbar

“…Passive thermal energy storage systems using microencapsulated phase change materials (PCMs) offer promise but face integration challenges in cementitious materials due to weakening mechanical strength, which arises from poor shell strength and weak interfacial bonding with cementitious phases. …”
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Unraveling the hidden universe of small proteins in bacterial genomes by Samuel Miravet‐Verde, Tony Ferrar, Guadalupe Espadas‐García, Rocco Mazzolini, Anas Gharrab, Eduard Sabido, Luis Serrano, Maria Lluch‐Senar

“…A functional study of SEPs highlighted an enrichment in the membrane, translation, metabolism, and nucleotide‐binding categories. Additionally, 9.7% of the SEPs included a N‐terminus predicted signal peptide. …”
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