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 Hepatic 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 Hepatic 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 Hepatic 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 Hepatic 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 Hepatic 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 Hepatic 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.
Hepatic sodium/bile acid cotransporter
partner:
Reaxense
upacc:
Q14973
UPID:
NTCP_HUMAN
Alternative names:
Cell growth-inhibiting gene 29 protein; Na(+)/bile acid cotransporter; Na(+)/taurocholate transport protein; Sodium/taurocholate cotransporting polypeptide; Solute carrier family 10 member 1
Alternative UPACC:
Q14973; B9EGB6; Q2TU29
Background:
The Hepatic sodium/bile acid cotransporter, also known as Solute carrier family 10 member 1, plays a pivotal role in the enterohepatic circulation of bile salts. This process is essential for the solubilization and absorption of dietary fats and fat-soluble vitamins. The transporter exhibits broad substrate specificity, handling various bile acids and non-bile acid organic compounds. It operates in concert with other transporters to ensure efficient bile acid recycling.
Therapeutic significance:
Familial Hypercholanemia, 2, a metabolic disorder characterized by increased plasma levels of conjugated bile salts, underscores the clinical importance of this transporter. Understanding its function could lead to novel therapeutic strategies for managing this condition and improving fat malabsorption issues.
