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 Ileal sodium/bile acid cotransporter 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 Ileal sodium/bile acid cotransporter 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 Ileal sodium/bile acid cotransporter, 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 Ileal sodium/bile acid cotransporter. 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 Ileal sodium/bile acid cotransporter. 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 Ileal sodium/bile acid cotransporter 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.
Ileal sodium/bile acid cotransporter
partner:
Reaxense
upacc:
Q12908
UPID:
NTCP2_HUMAN
Alternative names:
Apical sodium-dependent bile acid transporter; Ileal Na(+)/bile acid cotransporter; Ileal sodium-dependent bile acid transporter; Na(+)-dependent ileal bile acid transporter; Sodium/taurocholate cotransporting polypeptide, ileal; Solute carrier family 10 member 2
Alternative UPACC:
Q12908; A1L4F4; Q13839
Background:
The Ileal sodium/bile acid cotransporter, also known as Apical sodium-dependent bile acid transporter, plays a pivotal role in the reabsorption of bile acids from the small intestine, crucial for maintaining the body's bile acid pool and lipid digestion. It facilitates the transport of various bile acids, both unconjugated and conjugated, such as cholate and taurocholate, and collaborates with other transporters like NTCP, OST, and BSEP for efficient enterohepatic circulation of bile acids.
Therapeutic significance:
Mutations in this transporter are linked to Bile acid malabsorption, primary, 1, a disorder characterized by chronic diarrhea and malabsorption issues. Understanding the role of the Ileal sodium/bile acid cotransporter could open doors to potential therapeutic strategies for treating this condition and improving patient quality of life.
