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 Solute carrier family 22 member 4 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 Solute carrier family 22 member 4 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 Solute carrier family 22 member 4, 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 Solute carrier family 22 member 4. 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 Solute carrier family 22 member 4. 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 Solute carrier family 22 member 4 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.
Solute carrier family 22 member 4
partner:
Reaxense
upacc:
Q9H015
UPID:
S22A4_HUMAN
Alternative names:
Ergothioneine transporter; Organic cation/carnitine transporter 1
Alternative UPACC:
Q9H015; O14546
Background:
The Solute Carrier Family 22 Member 4, known as the Ergothioneine Transporter or Organic Cation/Carnitine Transporter 1, plays a crucial role in transporting endogenous and microbial zwitterions and organic cations. It is pivotal in the absorption of ergothioneine, a potent antioxidant, from the intestine and renal tubular cells into the liver, contributing to the body's steady-state ergothioneine level. Additionally, it facilitates the bidirectional transport of acetylcholine, influencing inflammation and oxidative stress control.
Therapeutic significance:
Given its involvement in controlling inflammation and oxidative stress, particularly through the transport of ergothioneine and acetylcholine, the Ergothioneine Transporter presents a promising target in the treatment of Rheumatoid arthritis, a disease marked by autoimmune features and joint inflammation. Understanding the role of this protein could open doors to potential therapeutic strategies.
