AIMC Topic: Proteolysis

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Deep learning guided design of protease substrates.

Nature communications
Proteases, enzymes that play critical roles in health and disease, exert their function through the cleavage of peptide bonds. Identifying substrates that are efficiently and selectively cleaved by target proteases is essential for studying protease ...

AI-driven discovery of dual antiaging and anti-AD therapeutics via PROTAC target deconvolution of a super-enhancer-regulated axis.

Science advances
The lack of safe, durable therapeutics that act against both biological aging and Alzheimer's disease is an unmet clinical need. To bridge this gap, we devised an artificial intelligence (AI)-enabled approach that pairs rapid compound triage with mec...

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...

Prediction of peptide cleavage sites using protein language models and graph neural networks.

Scientific reports
The growing interest in using peptide molecules as therapeutic agents, driven by their high selectivity and efficacy, has become a significant trend in the pharmaceutical industry. However, their oral administration remains challenging due to their l...

Hybrid plant-dairy cheese: Effects of lactic acid bacteria and plant proteins on composition, proteolysis, and flavor profile.

Food chemistry
In the search to improve the sustainability of the food supply chain, the market for plant-based cheese analogs is growing. However, sensory defects, particularly related to flavor, remain a challenge. Here we developed a hybrid plant-dairy cheese th...

DeepMaT: Prediction of Target Peptide Classification and Cleavage Site by Combining Mamba2 and Multiple Attention Mechanisms.

Journal of chemical information and modeling
Signal peptides and transit peptides are essential for directing mature proteins to their proper cellular locations, particularly through cleavage following transport. Although various prediction tools achieve strong performance in identifying and cl...

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...

A robust multiplex-DIA workflow profiles protein turnover regulations associated with cisplatin resistance and aneuploidy.

Nature communications
Quantifying protein turnover is fundamental to understanding cellular processes and advancing drug discovery. Multiplex-DIA mass spectrometry (MS), combined with dynamic SILAC labeling (pulse-SILAC, or pSILAC) reliably measures protein turnover and d...

Unlocking Antimicrobial Peptides: In Silico Proteolysis and Artificial Intelligence-Driven Discovery from Cnidarian Omics.

Molecules (Basel, Switzerland)
Overcoming the growing challenge of antimicrobial resistance (AMR), which affects millions of people worldwide, has driven attention for the exploration of marine-derived antimicrobial peptides (AMPs) for innovative solutions. Cnidarians, such as cor...