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 Iron-sulfur cluster co-chaperone protein HscB 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 Iron-sulfur cluster co-chaperone protein HscB 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 Iron-sulfur cluster co-chaperone protein HscB, 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 Iron-sulfur cluster co-chaperone protein HscB. 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 Iron-sulfur cluster co-chaperone protein HscB. 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 Iron-sulfur cluster co-chaperone protein HscB 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.
Iron-sulfur cluster co-chaperone protein HscB
partner:
Reaxense
upacc:
Q8IWL3
UPID:
HSC20_HUMAN
Alternative names:
DnaJ homolog subfamily C member 20
Alternative UPACC:
Q8IWL3; Q9BWS7
Background:
Iron-sulfur cluster co-chaperone protein HscB, also known as DnaJ homolog subfamily C member 20, plays a pivotal role in mitochondrial and cytoplasmic iron-sulfur cluster assembly. It acts as a co-chaperone, essential for the incorporation of iron-sulfur clusters into various proteins, including the succinate dehydrogenase complex, crucial for the mitochondrial electron transport chain. This protein's interaction with other components facilitates the complex formation necessary for iron-sulfur cluster insertion into key metabolic enzymes.
Therapeutic significance:
Given its critical role in hematopoiesis and its involvement in Anemia, sideroblastic, 5, a disorder characterized by systemic iron overload and ineffective erythropoiesis, Iron-sulfur cluster co-chaperone protein HscB represents a promising target for therapeutic intervention. Understanding the role of Iron-sulfur cluster co-chaperone protein HscB could open doors to potential therapeutic strategies for treating sideroblastic anemia and related mitochondrial dysfunctions.
