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 Serine/threonine-protein kinase Chk2 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 Serine/threonine-protein kinase Chk2 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 Serine/threonine-protein kinase Chk2, 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 Serine/threonine-protein kinase Chk2. 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 Serine/threonine-protein kinase Chk2. 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 Serine/threonine-protein kinase Chk2 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.
Serine/threonine-protein kinase Chk2
partner:
Reaxense
upacc:
O96017
UPID:
CHK2_HUMAN
Alternative names:
CHK2 checkpoint homolog; Cds1 homolog; Checkpoint kinase 2
Alternative UPACC:
O96017; A8K3Y9; B7ZBF3; B7ZBF4; B7ZBF5; Q6QA03; Q6QA04; Q6QA05; Q6QA06; Q6QA07; Q6QA08; Q6QA10; Q6QA11; Q6QA12; Q6QA13; Q9HBS5; Q9HCQ8; Q9UGF0; Q9UGF1
Background:
Serine/threonine-protein kinase Chk2, also known as CHK2 checkpoint homolog, plays a pivotal role in DNA damage response, cell cycle arrest, and apoptosis. It phosphorylates a range of effectors, including CDC25 phosphatases, BRCA2, p53/TP53, and MDM4, thereby regulating cell cycle progression, DNA repair, and apoptosis. Its activity is crucial for maintaining genomic stability and preventing the accumulation of DNA errors.
Therapeutic significance:
Chk2's involvement in Li-Fraumeni syndrome 2, prostate cancer, osteogenic sarcoma, and breast cancer underscores its critical role in cancer pathogenesis. Targeting Chk2 and its pathways offers a promising avenue for developing novel cancer therapies, particularly for tumors with genetic predispositions. Understanding the role of Serine/threonine-protein kinase Chk2 could open doors to potential therapeutic strategies.
