Sterile alpha motif domain-containing protein 9

Sterile alpha motif domain-containing protein 9 - Focused Library Design

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 Sterile alpha motif domain-containing protein 9 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 Sterile alpha motif domain-containing protein 9 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 Sterile alpha motif domain-containing protein 9, 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 Sterile alpha motif domain-containing protein 9. 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 Sterile alpha motif domain-containing protein 9. 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 Sterile alpha motif domain-containing protein 9 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.

Sterile alpha motif domain-containing protein 9

partner:

Reaxense

upacc:

Q5K651

UPID:

SAMD9_HUMAN

Alternative names:

Alternative UPACC:

Q5K651; A2RU68; Q5K649; Q6P080; Q75N21; Q8IVG6; Q9NXS8

Background:

Sterile alpha motif domain-containing protein 9 (SAMD9) is pivotal in antiviral defense, inflammation response, and possibly in preventing abnormal calcification, as suggested by its role in cytoplasmic antiviral granules formation and TNF-alpha signaling pathway. Its interaction with EGR1 and RGL2 indicates a broader regulatory function in cellular processes.

Therapeutic significance:

SAMD9 mutations are linked to severe disorders such as familial tumoral calcinosis, MIRAGE syndrome, and monosomy 7 myelodysplasia and leukemia syndrome 2. These associations underline the protein's critical role in disease mechanisms, offering a promising avenue for therapeutic interventions targeting SAMD9-related pathways.