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 Sigma non-opioid intracellular receptor 1 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 Sigma non-opioid intracellular receptor 1 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 Sigma non-opioid intracellular receptor 1, 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 Sigma non-opioid intracellular receptor 1. 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 Sigma non-opioid intracellular receptor 1. 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 Sigma non-opioid intracellular receptor 1 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.
Sigma non-opioid intracellular receptor 1
partner:
Reaxense
upacc:
Q99720
UPID:
SGMR1_HUMAN
Alternative names:
Aging-associated gene 8 protein; SR31747-binding protein; Sigma 1-type opioid receptor
Alternative UPACC:
Q99720; D3DRM7; O00673; O00725; Q0Z9W6; Q153Z1; Q2TSD1; Q53GN2; Q7Z653; Q8N7H3; Q9NYX0
Background:
Sigma non-opioid intracellular receptor 1, also known as Aging-associated gene 8 protein or Sigma 1-type opioid receptor, plays a pivotal role in lipid transport, receptor regulation, and cellular signaling. Its involvement in BDNF and EGF signaling, ion channel modulation, and calcium signaling underscores its multifaceted role in cell functions including proliferation, survival, and death. Additionally, it is crucial for mitochondrial axonal transport in motor neurons and protects against oxidative stress-induced cell death.
Therapeutic significance:
Linked to Amyotrophic lateral sclerosis 16 and Distal spinal muscular atrophy, autosomal recessive, 2, Sigma non-opioid intracellular receptor 1's genetic variants highlight its potential in neurodegenerative disease research. Understanding its role could open doors to novel therapeutic strategies, particularly in targeting motor neuron diseases and enhancing neuroprotective mechanisms.
