Statistical Molecular Interaction Fields: A Fast and Informative Tool for Characterizing RNA and Protein Binding Pockets

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Abstract Developing a physical understanding of the interactions between macro-molecular target and its ligands is crucial step in structure-based drug design. Although many tools exist to characterize protein-binding pockets silico, this not yet case for RNA, which has only recently been recognized as suitable small ligands. Molecular Interaction Fields (MIF) are useful tool given binding pocket. However, classical MIFs heavily rely on use probes, makes their calculations accurate but very specific partners question. We develop here simple version MIF, that we call Statistical (SMIF), based functional forms inspired by coarse-grained models parametrized PDB structures previous statistical analysis main form typical macromolecules, namely hydrogen bonding, stacking, hydrophobic interactions. show these fields, despite simplicity, informative overall agreement with pharmacophoric models. Thanks carefully optimized code, our fast can be performed bulk large set or even full macromolecule. As shown few representative examples, latter possibility opens way systems 20 80 k atoms relation surrounding environment, i.e., lipidic membrane, ligand, another macromolecular partner, allowing detailed visualization possible

Language: Английский

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Structural and Biological Investigation of (E)-2-((2-Butyl-4-Chloro-1H-Imidazol-5-yl)methylene)hydrazine-1-carbothioamide: Synthesis, Structural Insights, Antitubercular Screening, Molecular Docking, DFT, and ADME Studies

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 142560 - 142560

Published: May 1, 2025

Language: Английский

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Recent advances from computer-aided drug design to artificial intelligence drug design

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 15(12), P. 3978 - 4000

Published: Jan. 1, 2024

CADD and AIDD contribute to the drug discovery.

Language: Английский

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Specific staining and precise killing of cancer cells through fusion of pharmaceutical chemistry and π-bridge effect design philosophy

Science China Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract The development of an advanced phototheranostic platform that combines imaging and therapy in a single agent is appealing yet challenging task. In this study, we successfully constructed three novel fluorescent probes by leveraging pharmaceutical chemistry the design philosophy π -bridge effect. Through systematic comparative analysis their fluorescence properties, water solubility, molecular conformation, electrostatic potential, revealed fundamental principles governing optical behavior biological selectivity these probes. Notably, probe TPhIQ-CNTh demonstrated extended near-infrared region, significant aggregation-induced emission (AIE) effect, ability to distinguish tumor cells from normal cells. Moreover, it efficiently generated reactive oxygen species (ROS) specifically labeled lipid droplets, enabling precise staining killing cancer This study presents practical strategy for designing treatments integrate efficient imaging-guided photodynamic (PDT) harnessing unique properties AIE materials.

Language: Английский

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Genetic targets related to aging for the treatment of coronary artery disease

BMC Medical Genomics, Journal Year: 2025, Volume and Issue: 18(1)

Published: April 9, 2025

Coronary Artery Disease (CAD) is the most common cardiovascular disease worldwide, threatening human health, quality of life and longevity. Aging a dominant risk factor for CAD. This study aims to investigate potential mechanisms aging-related genes CAD, make molecular drug predictions that will contribute diagnosis treatment. We downloaded gene expression profile circulating leukocytes in CAD patients (GSE12288) from Gene Expression Omnibus database, obtained differentially expressed aging through "limma" package GenaCards tested their biological functions. Further screening related characteristic (ARCGs) using least absolute shrinkage selection operator random forest, generating nomogram charts ROC curves evaluating diagnostic efficacy. Immune cells were estimated by ssGSEA, then combine ARCGs with immune clinical indicators based on Pearson correlation analysis. Unsupervised cluster analysis was used construct clusters assess functional characteristics between clusters. The DSigDB database employed explore targeted drugs ARCGs, docking carried out Autodock Vina. Finally, single-cell data (GSE159677) arterial intima further signature different cell subpopulations. identified 8 associated which HIF1A FGFR3 up while NOX4, TCF7L2, HK3, CDK18, TFAP4, ITPK1 down patients. Based this, can be divided into two clusters, among A mainly involves pathways such as ECM receptor interaction focal adhesion; B amimo sugar nucleotide metabolism pyrimidine metabolism. In addition, results showed retinoic acid resveratrol had good binding affinity targets genes. ITPK1, specifically types atherosclerotic tissues. Our several may involved pathogenesis progression Further, candidate molecule inhibiting these targets.

Language: Английский

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Comprehensive Exploration of Thiophene-Tagged 2-(2-Hydrazinyl)thiazole Derivatives: Synthesis, Structural Characterization, Antimicrobial Potential, and Computational Insights

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 142453 - 142453

Published: April 1, 2025

Language: Английский

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Current perspectives in drug targeting intrinsically disordered proteins and biomolecular condensates

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: May 5, 2025

Intrinsically disordered proteins (IDPs) and biomolecular condensates are critical for cellular processes physiological functions. Abnormal can cause diseases such as cancer neurodegenerative disorders. IDPs, including intrinsically regions (IDRs), were previously considered undruggable due to their lack of stable binding pockets. However, recent evidence indicates that targeting them influence processes. This review explores current strategies target IDPs condensates, potential improvements, the challenges opportunities in this evolving field.

Language: Английский

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Phytochemical screening and Spectroscopic characterization of cannabis sativa L, cultivated in Mt Kenya region, Kenya

Published: May 7, 2025

The aim of this research is to determine the phytochemicals and characterize cannabis sativa leaf extracts because they are one consumed with HPLC, GC-MS, VV-VIS, FT-IR AAS. phytochemical screening showed that phenols tannins ware determinant phytochemicals, analyzed functional group present, HPLC Catechin acid di-hydrate was major compound in dichloromethane extract ethanolic extract, while Naringin component aqueous GC-MS palmitic , Linoleic 7-oxtadecanoic Linolenic it confirmed by UV-VIS AAS Cannabis sativa L. found contain higher levels heavy metals Fe, Zn, Mn, Cu.

Language: Английский

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Design strategies and recent development of bioactive modulators for glutamine transporters

Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(2), P. 103880 - 103880

Published: Jan. 11, 2024

Language: Английский

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Importance of Inter-residue Contacts for Understanding Protein Folding and Unfolding Rates, Remote Homology, and Drug Design

Molecular Biotechnology, Journal Year: 2024, Volume and Issue: 67(3), P. 862 - 884

Published: March 18, 2024

Language: Английский

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