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 Oxysterols receptor LXR-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 Oxysterols receptor LXR-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 Oxysterols receptor LXR-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 Oxysterols receptor LXR-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 Oxysterols receptor LXR-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 Oxysterols receptor LXR-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.
Oxysterols receptor LXR-beta
partner:
Reaxense
upacc:
P55055
UPID:
NR1H2_HUMAN
Alternative names:
Liver X receptor beta; Nuclear receptor NER; Nuclear receptor subfamily 1 group H member 2; Ubiquitously-expressed nuclear receptor
Alternative UPACC:
P55055; A8K490; B4DNM6; E7EWA6; Q12970; Q5I0Y1
Background:
Oxysterols receptor LXR-beta, also known as Liver X receptor beta, plays a pivotal role in cholesterol homeostasis, lipid metabolism, and inflammatory processes. It functions by binding to specific DNA sequences, regulating the expression of genes involved in lipid uptake, and modulating the inflammatory response in hepatocytes. Its activity is enhanced by ligands and involves critical interactions with proteins such as MYLIP for LDLR regulation, and LPCAT3 for lipid remodeling.
Therapeutic significance:
Understanding the role of Oxysterols receptor LXR-beta could open doors to potential therapeutic strategies. Its involvement in lipid metabolism and inflammation highlights its potential as a target for treating metabolic disorders and inflammatory diseases. The receptor's ability to modulate cholesterol levels and inflammatory responses presents a promising avenue for drug discovery aimed at cardiovascular diseases and liver conditions.
