AIMC Topic: Ubiquitin-Protein Ligases

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How Feasible Is Docking of PROTACs to POI-E3L Complexes? Testing Physics-Based and ML-Based Docking Tools.

Journal of chemical information and modeling
Targeted protein degradation (TPD) is an innovative drug discovery approach that leverages small molecules to induce proximity between a protein of interest (POI) and an E3 ubiquitin ligase (E3L) for selective degradation. Among TPD modalities, prote...

Molecular Glues in Immunotherapy: Fine-Tuning Immune Responses for Precision Medicine.

International immunopharmacology
Molecular glues are a new class of tiny compounds that can rewire protein-protein interactions, providing a very selective mechanism to modify immunological signalling pathways. These substances allow immune regulators to be selectively degraded or s...

Phenotypic Screening for Targeted Protein Degradation: Strategies, Challenges, and Emerging Opportunities.

Journal of medicinal chemistry
Phenotypic screening is undergoing a resurgence in the field of targeted protein degradation as a powerful complement to target-based approaches, which are often constrained by requirements for detailed structural and ligand-binding information. Phen...

SE(3)-equivariant ternary complex prediction towards target protein degradation.

Nature communications
Targeted protein degradation (TPD) has rapidly emerged as a powerful modality for drugging previously "undruggable" proteins. TPD employs small molecules like PROTACs and molecular glue degraders (MGD) to induce target protein degradation via the for...

Therapeutic potential of allosteric HECT E3 ligase inhibition.

Cell
Targeting ubiquitin E3 ligases is therapeutically attractive; however, the absence of an active-site pocket impedes computational approaches for identifying inhibitors. In a large, unbiased biochemical screen, we discover inhibitors that bind a crypt...

An artificial intelligence accelerated virtual screening platform for drug discovery.

Nature communications
Structure-based virtual screening is a key tool in early drug discovery, with growing interest in the screening of multi-billion chemical compound libraries. However, the success of virtual screening crucially depends on the accuracy of the binding p...

Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells.

Science (New York, N.Y.)
Chemical modulation of proteins enables a mechanistic understanding of biology and represents the foundation of most therapeutics. However, despite decades of research, 80% of the human proteome lacks functional ligands. Chemical proteomics has advan...

PROTACable Is an Integrative Computational Pipeline of 3-D Modeling and Deep Learning To Automate the De Novo Design of PROTACs.

Journal of chemical information and modeling
Proteolysis-targeting chimeras (PROTACs) that engage two biological targets at once are a promising technology in degrading clinically relevant protein targets. Since factors that influence the biological activities of PROTACs are more complex than t...

Discovery of a Novel DCAF1 Ligand Using a Drug-Target Interaction Prediction Model: Generalizing Machine Learning to New Drug Targets.

Journal of chemical information and modeling
DCAF1 functions as a substrate recruitment subunit for the RING-type CRL4 and the HECT family EDVP E3 ubiquitin ligases. The WDR domain of DCAF1 serves as a binding platform for substrate proteins and is also targeted by HIV and SIV lentiviral adapto...

Bifunctional robots inducing targeted protein degradation.

European journal of medicinal chemistry
The gaining importance of Targeted Protein Degradation (TPD) and PROTACs (PROteolysis-TArgeting Chimeras) have drawn the scientific community's attention. PROTACs are considered bifunctional robots owing to their avidity for the protein of interest (...