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 Amiloride-sensitive sodium channel subunit alpha 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 Amiloride-sensitive sodium channel subunit alpha 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 Amiloride-sensitive sodium channel subunit alpha, 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 Amiloride-sensitive sodium channel subunit alpha. 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 Amiloride-sensitive sodium channel subunit alpha. 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 Amiloride-sensitive sodium channel subunit alpha 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.
Amiloride-sensitive sodium channel subunit alpha
partner:
Reaxense
upacc:
P37088
UPID:
SCNNA_HUMAN
Alternative names:
Alpha-NaCH; Epithelial Na(+) channel subunit alpha; Nonvoltage-gated sodium channel 1 subunit alpha; SCNEA
Alternative UPACC:
P37088; A5X2U9; B4E2Q5; C5HTZ0; O43271; Q6GSQ6; Q9UM64
Background:
The Amiloride-sensitive sodium channel subunit alpha, also known as Alpha-NaCH, SCNEA, and Nonvoltage-gated sodium channel 1 subunit alpha, plays a pivotal role in the regulation of sodium permeability across epithelial cells. This protein facilitates the electrodiffusion of sodium, crucial for maintaining electrolyte balance, blood pressure, airway surface liquid homeostasis, and taste perception. Its expression in kidney, colon, lung, and eccrine sweat glands underscores its integral function in sodium reabsorption and fluid balance.
Therapeutic significance:
Mutations in the Amiloride-sensitive sodium channel subunit alpha are linked to several diseases, including Pseudohypoaldosteronism 1B1, autosomal recessive, characterized by salt wasting and severe electrolyte imbalance. Additionally, it is associated with Bronchiectasis with or without elevated sweat chloride 2, and Liddle syndrome 3, highlighting its role in respiratory and blood pressure disorders. Understanding the molecular mechanisms of this channel could lead to targeted therapies for these conditions.
