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 Terminal nucleotidyltransferase 5A 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 Terminal nucleotidyltransferase 5A 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 Terminal nucleotidyltransferase 5A, 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 Terminal nucleotidyltransferase 5A. 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 Terminal nucleotidyltransferase 5A. 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 Terminal nucleotidyltransferase 5A 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.
Terminal nucleotidyltransferase 5A
partner:
Reaxense
upacc:
Q96IP4
UPID:
TET5A_HUMAN
Alternative names:
HBV X-transactivated gene 11 protein; HBV XAg-transactivated protein 11
Alternative UPACC:
Q96IP4; A8K7U4; Q5TF86; Q8NFZ9; Q9BW32; Q9NXV5
Background:
Terminal nucleotidyltransferase 5A, also known as HBV X-transactivated gene 11 protein, plays a crucial role in bone health. It functions as a cytoplasmic non-canonical poly(A) RNA polymerase, catalyzing the transfer of adenosine molecules to mRNA poly(A) tails. This process is vital for the polyadenylation of mRNA encoding extracellular matrix constituents and other genes essential for bone mineralization.
Therapeutic significance:
The protein's involvement in Osteogenesis imperfecta 18, a severe connective tissue disorder characterized by bone fragility, underscores its therapeutic potential. Understanding the role of Terminal nucleotidyltransferase 5A could open doors to potential therapeutic strategies for treating bone-related diseases.
