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 Proteasome subunit beta type-8 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 Proteasome subunit beta type-8 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 Proteasome subunit beta type-8, 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 Proteasome subunit beta type-8. 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 Proteasome subunit beta type-8. 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 Proteasome subunit beta type-8 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.
Proteasome subunit beta type-8
partner:
Reaxense
upacc:
P28062
UPID:
PSB8_HUMAN
Alternative names:
Low molecular mass protein 7; Macropain subunit C13; Multicatalytic endopeptidase complex subunit C13; Proteasome component C13; Proteasome subunit beta-5i; Really interesting new gene 10 protein
Alternative UPACC:
P28062; B0UZC0; Q29824; Q5JNW6; Q5QNR8; Q96J48
Background:
Proteasome subunit beta type-8, also known as PSMB8, plays a pivotal role in the proteasome complex, a key enzyme in protein degradation. It is involved in antigen processing, generation of spliced peptides, and plays a crucial role in the immune response and apoptosis. PSMB8 is essential for the differentiation of preadipocytes into adipocytes and has a significant role in the inflammatory response pathway.
Therapeutic significance:
The mutation in PSMB8 is linked to Proteasome-associated autoinflammatory syndrome 1, a disorder marked by recurrent fever, joint stiffness, and severe skin lesions. Understanding the role of PSMB8 could open doors to potential therapeutic strategies for treating this autoinflammatory disorder and possibly other conditions related to immune dysregulation.
