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 Neutrophil cytosol factor 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 Neutrophil cytosol factor 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 Neutrophil cytosol factor 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 Neutrophil cytosol factor 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 Neutrophil cytosol factor 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 Neutrophil cytosol factor 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.
Neutrophil cytosol factor 1
partner:
Reaxense
upacc:
P14598
UPID:
NCF1_HUMAN
Alternative names:
47 kDa autosomal chronic granulomatous disease protein; 47 kDa neutrophil oxidase factor; NCF-47K; Neutrophil NADPH oxidase factor 1; Nox organizer 2; Nox-organizing protein 2; SH3 and PX domain-containing protein 1A; p47-phox
Alternative UPACC:
P14598; A6NEH2; A8K7S9; O43842; Q2PP07; Q53FR5; Q9BU90; Q9BXI7; Q9BXI8; Q9UDV9; Q9UMU2
Background:
Neutrophil cytosol factor 1 (NCF1), also known by several alternative names such as p47-phox, plays a pivotal role in the immune system's response to infection. It is a crucial component of the NADPH oxidase complex, which is essential for the production of reactive oxygen species (ROS) by phagocytes. These ROS are vital for the destruction of invading pathogens, highlighting NCF1's role in host defense mechanisms.
Therapeutic significance:
Mutations in NCF1 are linked to Granulomatous disease, chronic, autosomal recessive, 1, characterized by severe infections and chronic inflammation due to impaired ROS production. Understanding the role of NCF1 could open doors to potential therapeutic strategies for enhancing host defense mechanisms against pathogens.
