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 Ammonium transporter Rh type A 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 Ammonium transporter Rh type A 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 Ammonium transporter Rh type A, 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 Ammonium transporter Rh type A. 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 Ammonium transporter Rh type A. 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 Ammonium transporter Rh type A 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.
Ammonium transporter Rh type A
partner:
Reaxense
upacc:
Q02094
UPID:
RHAG_HUMAN
Alternative names:
Erythrocyte membrane glycoprotein Rh50; Erythrocyte plasma membrane 50 kDa glycoprotein; Rhesus blood group family type A glycoprotein; Rhesus blood group-associated ammonia channel; Rhesus blood group-associated glycoprotein
Alternative UPACC:
Q02094; B2R8T8; O43514; O43515; Q7L8L3; Q9H454
Background:
The Ammonium transporter Rh type A, also known as Erythrocyte membrane glycoprotein Rh50, plays a pivotal role in the stability and shape of the erythrocyte membrane. This protein is a component of the ankyrin-1 complex and is involved in the transport of ammonium and CO2 across the erythrocyte membrane. Its ability to leak monovalent cations and regulate RHD membrane expression underscores its significance in erythrocyte physiology and the rhesus blood group antigen expression.
Therapeutic significance:
Given its crucial role in erythrocyte membrane stability and ion transport, the Ammonium transporter Rh type A is linked to diseases such as Regulator type Rh-null hemolytic anemia and Overhydrated hereditary stomatocytosis. Understanding the role of this protein could open doors to potential therapeutic strategies for these red blood cell disorders.
