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 NADH-cytochrome b5 reductase 3 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 NADH-cytochrome b5 reductase 3 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 NADH-cytochrome b5 reductase 3, 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 NADH-cytochrome b5 reductase 3. 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 NADH-cytochrome b5 reductase 3. 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 NADH-cytochrome b5 reductase 3 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.
NADH-cytochrome b5 reductase 3
partner:
Reaxense
upacc:
P00387
UPID:
NB5R3_HUMAN
Alternative names:
Diaphorase-1
Alternative UPACC:
P00387; B1AHF2; B7Z7L3; O75675; Q8TDL8; Q8WTS8; Q9UEN4; Q9UEN5; Q9UL55; Q9UL56
Background:
NADH-cytochrome b5 reductase 3, also known as Diaphorase-1, plays a crucial role in cellular processes by catalyzing the reduction of cytochrome b5 using NADH as the electron donor. This enzyme is pivotal in maintaining the balance of electron transfer reactions within cells.
Therapeutic significance:
Methemoglobinemia CYB5R3-related, a condition marked by reduced oxygen transport in the blood due to excessive methemoglobin, is directly linked to mutations in the gene encoding NADH-cytochrome b5 reductase 3. Understanding the enzyme's function could lead to targeted therapies for this disease, enhancing patient outcomes.
