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 Optineurin 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 Optineurin 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 Optineurin, 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 Optineurin. 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 Optineurin. 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 Optineurin 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.
Optineurin
partner:
Reaxense
upacc:
Q96CV9
UPID:
OPTN_HUMAN
Alternative names:
E3-14.7K-interacting protein; Huntingtin yeast partner L; Huntingtin-interacting protein 7; Huntingtin-interacting protein L; NEMO-related protein; Optic neuropathy-inducing protein; Transcription factor IIIA-interacting protein
Alternative UPACC:
Q96CV9; B3KP00; D3DRS4; D3DRS8; Q5T672; Q5T673; Q5T674; Q5T675; Q7LDL9; Q8N562; Q9UET9; Q9UEV4; Q9Y218
Background:
Optineurin, encoded by the gene symbolized as Q96CV9, is pivotal in cellular processes including Golgi complex maintenance, membrane trafficking, and exocytosis. It facilitates the interaction between myosin VI and Rab8, crucial for Golgi ribbon formation and innate immune response activation against viral infections. Optineurin's role extends to neuroprotection in the eye and optic nerve, potentially through regulating membrane trafficking and cellular morphogenesis alongside Rab8 and huntingtin.
Therapeutic significance:
Optineurin's involvement in diseases such as primary open angle glaucoma, normal pressure glaucoma, and amyotrophic lateral sclerosis 12 highlights its therapeutic potential. Understanding the multifaceted role of Optineurin in these conditions could pave the way for innovative therapeutic strategies, offering hope for patients suffering from these debilitating diseases.
