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 Interferon gamma 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 Interferon gamma 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 Interferon gamma 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 Interferon gamma 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 Interferon gamma 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 Interferon gamma 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.
Interferon gamma receptor 1
partner:
Reaxense
upacc:
P15260
UPID:
INGR1_HUMAN
Alternative names:
CDw119; Interferon gamma receptor alpha-chain
Alternative UPACC:
P15260; B4DFT7; E1P587; Q53Y96
Background:
Interferon gamma receptor 1 (IFNGR1), also known as CDw119, plays a pivotal role in immune responses against infections and tumors. It forms a functional receptor with IFNGR2, crucial for activating immune cells and enhancing antigen presentation. Upon binding with interferon gamma, IFNGR1 initiates a cascade involving JAK1 and JAK2 phosphorylation, leading to STAT1 activation and gene transcription essential for antimicrobial, antiviral, and antitumor responses.
Therapeutic significance:
Mutations in IFNGR1 are linked to Immunodeficiency 27A and 27B, conditions characterized by impaired interferon-gamma mediated immunity, leading to susceptibility to mycobacterial diseases. Understanding the role of IFNGR1 could open doors to potential therapeutic strategies for these immunodeficiencies, offering hope for targeted treatments that restore immune function and prevent severe infections.
