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 NLR family CARD domain-containing protein 4 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 NLR family CARD domain-containing protein 4 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 NLR family CARD domain-containing protein 4, 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 NLR family CARD domain-containing protein 4. 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 NLR family CARD domain-containing protein 4. 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 NLR family CARD domain-containing protein 4 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.
NLR family CARD domain-containing protein 4
partner:
Reaxense
upacc:
Q9NPP4
UPID:
NLRC4_HUMAN
Alternative names:
CARD, LRR, and NACHT-containing protein; Caspase recruitment domain-containing protein 12; Ice protease-activating factor
Alternative UPACC:
Q9NPP4; A8K9F8; B2RBQ3; B3KTF0; D6W580; Q96J81; Q96J82; Q96J83
Background:
NLR family CARD domain-containing protein 4, also known as NLRC4, plays a pivotal role in the immune system. It is a key component of inflammasomes, specialized protein complexes that detect pathogenic microorganisms and damaged cellular components to initiate an inflammatory response. NLRC4 specifically responds to proteins from pathogenic bacteria and fungi, leading to the activation of caspase-1, cytokine production, and macrophage pyroptosis.
Therapeutic significance:
NLRC4 is implicated in autoinflammatory diseases such as Autoinflammation with infantile enterocolitis and Familial cold autoinflammatory syndrome 4. These conditions are characterized by episodes of fever, inflammation, and organ-specific symptoms, caused by genetic variants affecting NLRC4. Understanding the role of NLRC4 could open doors to potential therapeutic strategies for these autoinflammatory disorders.
