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 Beta-hexosaminidase subunit beta 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 Beta-hexosaminidase subunit beta 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 Beta-hexosaminidase subunit beta, 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 Beta-hexosaminidase subunit beta. 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 Beta-hexosaminidase subunit beta. 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 Beta-hexosaminidase subunit beta 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.
Beta-hexosaminidase subunit beta
partner:
Reaxense
upacc:
P07686
UPID:
HEXB_HUMAN
Alternative names:
Beta-N-acetylhexosaminidase subunit beta; Cervical cancer proto-oncogene 7 protein; N-acetyl-beta-glucosaminidase subunit beta
Alternative UPACC:
P07686
Background:
Beta-hexosaminidase subunit beta, also known as Beta-N-acetylhexosaminidase subunit beta, plays a crucial role in the hydrolysis of the non-reducing end N-acetyl-D-hexosamine of glycoconjugates. This enzyme is pivotal in the degradation of GM2 gangliosides, with its isozyme A being specifically responsible for this process in the presence of GM2A. Its presence in non-activated oocytes and subsequent release during oocyte activation highlights its role in fertilization, particularly in preventing polyspermy by inactivating the sperm galactosyltransferase-binding site.
Therapeutic significance:
The enzyme's deficiency is linked to GM2-gangliosidosis 2, an autosomal recessive lysosomal storage disease characterized by the accumulation of GM2 gangliosides in neuronal cells. This condition underscores the enzyme's therapeutic significance, as understanding its function and the genetic variants affecting it could lead to targeted treatments for this debilitating disease.
