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 Bile salt export pump 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 Bile salt export pump 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 Bile salt export pump, 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 Bile salt export pump. 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 Bile salt export pump. 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 Bile salt export pump 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.
Bile salt export pump
partner:
Reaxense
upacc:
O95342
UPID:
ABCBB_HUMAN
Alternative names:
ATP-binding cassette sub-family B member 11
Alternative UPACC:
O95342; Q53TL2; Q9UNB2
Background:
The Bile Salt Export Pump (BSEP), also known as ATP-binding cassette sub-family B member 11, plays a crucial role in the transport of major hydrophobic bile salts across the canalicular membrane of hepatocytes in an ATP-dependent manner. This process is vital for hepatic bile acid homeostasis, impacting lipid homeostasis through regulation of biliary lipid secretion. BSEP's ability to transport taurine-conjugated bile salts more efficiently than glycine-conjugated ones, alongside its role in the biliary excretion of non-bile acid compounds like pravastatin and fexofenadine, underscores its multifunctional nature.
Therapeutic significance:
BSEP is implicated in two significant liver disorders: Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2), a severe condition leading to liver failure before adulthood, and Benign Recurrent Intrahepatic Cholestasis type 2 (BRIC2), characterized by intermittent cholestasis episodes. Understanding the role of BSEP in these diseases could pave the way for developing targeted therapies, offering hope for patients suffering from these debilitating conditions.
