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-ubiquinone oxidoreductase chain 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 NADH-ubiquinone oxidoreductase chain 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 NADH-ubiquinone oxidoreductase chain 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 NADH-ubiquinone oxidoreductase chain 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 NADH-ubiquinone oxidoreductase chain 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 NADH-ubiquinone oxidoreductase chain 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.
NADH-ubiquinone oxidoreductase chain 1
partner:
Reaxense
upacc:
P03886
UPID:
NU1M_HUMAN
Alternative names:
NADH dehydrogenase subunit 1
Alternative UPACC:
P03886; C0JKH6; Q37523
Background:
NADH-ubiquinone oxidoreductase chain 1, also known as NADH dehydrogenase subunit 1, plays a pivotal role in cellular energy production. It is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), essential for electron transfer from NADH through the respiratory chain, utilizing ubiquinone as an electron acceptor.
Therapeutic significance:
This protein's malfunction is linked to severe diseases such as Leber hereditary optic neuropathy, mitochondrial encephalomyopathy with lactic acidosis, Alzheimer disease mitochondrial, and Type 2 diabetes mellitus. Understanding its role could lead to novel therapeutic strategies for these conditions.
