Serine/threonine-protein kinase/endoribonuclease IRE1

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 Serine/threonine-protein kinase/endoribonuclease IRE1 therapeutic significance, existing small molecule ligands, relevant off-targets, and protein-protein interactions.

2. AI-Driven Conformational Ensemble Generation

Starting from the initial protein structure, we employed advanced AI algorithms to predict alternative functional states of Serine/threonine-protein kinase/endoribonuclease IRE1, 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.

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.

4. AI-Powered Virtual Screening

Our ecosystem is equipped to perform AI-driven virtual screening on Serine/threonine-protein kinase/endoribonuclease IRE1. 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 Serine/threonine-protein kinase/endoribonuclease IRE1. This approach allows us to achieve an excellent hit rate and to identify compounds ready for advanced lead discovery and optimization.

Receptor.AI, in partnership with Reaxense, developed a next-generation technology for on-demand focused library design to enable extensive target exploration.