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 Sodium channel protein type 8 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 Sodium channel protein type 8 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 Sodium channel protein type 8 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 Sodium channel protein type 8 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 Sodium channel protein type 8 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 Sodium channel protein type 8 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.
Sodium channel protein type 8 subunit alpha
partner:
Reaxense
upacc:
Q9UQD0
UPID:
SCN8A_HUMAN
Alternative names:
Sodium channel protein type VIII subunit alpha; Voltage-gated sodium channel subunit alpha Nav1.6
Alternative UPACC:
Q9UQD0; B9VWG8; O95788; Q9NYX2; Q9UPB2
Background:
The Sodium channel protein type 8 subunit alpha, also known as Voltage-gated sodium channel subunit alpha Nav1.6, plays a crucial role in mediating the voltage-dependent sodium ion permeability of excitable membranes. This protein transitions between opened or closed conformations in response to voltage differences across the membrane, forming a sodium-selective channel that facilitates Na(+) ions movement according to their electrochemical gradient. Additionally, it has a role in macrophages and melanoma cells, influencing podosome and invadopodia formation.
Therapeutic significance:
The Sodium channel protein type 8 subunit alpha is implicated in various neurological disorders, including Cognitive impairment with or without cerebellar ataxia, Developmental and epileptic encephalopathy 13, Benign familial infantile seizures, and Familial myoclonus 2. These associations highlight its potential as a target for therapeutic strategies aimed at treating these conditions.
