AI-ACCELERATED DRUG DISCOVERY
Available from Reaxense
This protein is integrated into the Receptor.AI ecosystem as a prospective target with high therapeutic potential. We performed a comprehensive characterization of Ubiquitin carboxyl-terminal hydrolase 48 including:
1. LLM-powered literature research
Our custom-tailored LLM extracted and formalized all relevant information about the protein from a large set of structured and unstructured data sources and stored it in the form of a Knowledge Graph. This comprehensive analysis allowed us to gain insight into Ubiquitin carboxyl-terminal hydrolase 48 therapeutic significance, existing small molecule ligands, relevant off-targets, and protein-protein interactions.
Fig. 1. Preliminary target research workflow
2. AI-Driven Conformational Ensemble Generation
Starting from the initial protein structure, we employed advanced AI algorithms to predict alternative functional states of Ubiquitin carboxyl-terminal hydrolase 48, including large-scale conformational changes along "soft" collective coordinates. Through molecular simulations with AI-enhanced sampling and trajectory clustering, we explored the broad conformational space of the protein and identified its representative structures. Utilizing diffusion-based AI models and active learning AutoML, we generated a statistically robust ensemble of equilibrium protein conformations that capture the receptor's full dynamic behavior, providing a robust foundation for accurate structure-based drug design.
Fig. 2. AI-powered molecular dynamics simulations workflow
3. Binding pockets identification and characterization
We employed the AI-based pocket prediction module to discover orthosteric, allosteric, hidden, and cryptic binding pockets on the protein’s surface. Our technique integrates the LLM-driven literature search and structure-aware ensemble-based pocket detection algorithm that utilizes previously established protein dynamics. Tentative pockets are then subject to AI scoring and ranking with simultaneous detection of false positives. In the final step, the AI model assesses the druggability of each pocket enabling a comprehensive selection of the most promising pockets for further targeting.
Fig. 3. AI-based binding pocket detection workflow
4. AI-Powered Virtual Screening
Our ecosystem is equipped to perform AI-driven virtual screening on Ubiquitin carboxyl-terminal hydrolase 48. With access to a vast chemical space and cutting-edge AI docking algorithms, we can rapidly and reliably predict the most promising, novel, diverse, potent, and safe small molecule ligands of Ubiquitin carboxyl-terminal hydrolase 48. This approach allows us to achieve an excellent hit rate and to identify compounds ready for advanced lead discovery and optimization.
Fig. 4. The screening workflow of Receptor.AI
Receptor.AI, in partnership with Reaxense, developed a next-generation technology for on-demand focused library design to enable extensive target exploration.
The focused library for Ubiquitin carboxyl-terminal hydrolase 48 includes a list of the most effective modulators, each annotated with 38 ADME-Tox and 32 physicochemical and drug-likeness parameters. Furthermore, each compound is shown with its optimal docking poses, affinity scores, and activity scores, offering a detailed summary.
Ubiquitin carboxyl-terminal hydrolase 48
partner:
Reaxense
upacc:
Q86UV5
UPID:
UBP48_HUMAN
Alternative names:
Deubiquitinating enzyme 48; Ubiquitin thioesterase 48; Ubiquitin-specific peptidase 48; Ubiquitin-specific protease 48; Ubiquitin-specific-processing protease 48
Alternative UPACC:
Q86UV5; B7ZKS7; Q2M3I4; Q5SZI4; Q5T3T5; Q6NX53; Q8N3F6; Q96F64; Q96IQ3; Q9H5N3; Q9H5T7; Q9NUJ6; Q9NXR0
Background:
Ubiquitin carboxyl-terminal hydrolase 48, known by alternative names such as Deubiquitinating enzyme 48 and Ubiquitin-specific protease 48, plays a crucial role in protein degradation pathways. It recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin, involved in processing poly-ubiquitin precursors and ubiquitinated proteins. This enzyme is pivotal in regulating NF-kappa-B activation and may influence postsynaptic sites.
Therapeutic significance:
Linked to Deafness, autosomal dominant, 85, a condition characterized by progressive sensorineural hearing loss, Ubiquitin carboxyl-terminal hydrolase 48's involvement suggests potential therapeutic targets. Understanding its role could open doors to innovative treatments for hearing loss and related neural disorders.
