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 Telomere length regulation protein TEL2 homolog 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 Telomere length regulation protein TEL2 homolog 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 Telomere length regulation protein TEL2 homolog, 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 Telomere length regulation protein TEL2 homolog. 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 Telomere length regulation protein TEL2 homolog. 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 Telomere length regulation protein TEL2 homolog 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.
Telomere length regulation protein TEL2 homolog
partner:
Reaxense
upacc:
Q9Y4R8
UPID:
TELO2_HUMAN
Alternative names:
Protein clk-2 homolog
Alternative UPACC:
Q9Y4R8; D3DU73; O75168; Q7LDV4; Q9BR21
Background:
The Telomere length regulation protein TEL2 homolog, also known as Protein clk-2 homolog, plays a pivotal role in the DNA damage response (DDR). It is a crucial component of the TTT complex, essential for stabilizing PIKK family proteins, thereby facilitating cellular resistance to DNA damage from ionizing radiation, ultraviolet light, and mitomycin C. Additionally, it aids in the proper folding of newly synthesized PIKKs through its interaction with the TTT complex and HSP90, and is instrumental in regulating the assembly, stability, and activity of mTORC1 and mTORC2 complexes, which are key regulators of cell growth and survival.
Therapeutic significance:
Given its involvement in You-Hoover-Fong syndrome, characterized by severe developmental delays, intellectual disability, and congenital heart disease, understanding the role of Telomere length regulation protein TEL2 homolog could pave the way for novel therapeutic strategies targeting this syndrome and potentially other related disorders.
