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 Chromodomain-helicase-DNA-binding protein 8 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 Chromodomain-helicase-DNA-binding protein 8 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 Chromodomain-helicase-DNA-binding protein 8, 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 Chromodomain-helicase-DNA-binding protein 8. 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 Chromodomain-helicase-DNA-binding protein 8. 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 Chromodomain-helicase-DNA-binding protein 8 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.
Chromodomain-helicase-DNA-binding protein 8
partner:
Reaxense
upacc:
Q9HCK8
UPID:
CHD8_HUMAN
Alternative names:
ATP-dependent helicase CHD8; Helicase with SNF2 domain 1
Alternative UPACC:
Q9HCK8; Q4G0D8; Q68DQ0; Q6DKH9; Q6P440; Q6ZNL7; Q8N3Z9; Q8NCY4; Q8TBR9; Q96F26
Background:
Chromodomain-helicase-DNA-binding protein 8 (CHD8), also known as ATP-dependent helicase CHD8, plays a pivotal role in DNA repair, transcription regulation, and chromatin remodeling. It acts as a transcription repressor, regulating gene expression by remodeling chromatin structure and recruiting histone H1. CHD8 negatively regulates the Wnt signaling pathway and STAT3 activity, influencing cell cycle, neuronal differentiation, and DNA repair.
Therapeutic significance:
CHD8 is linked to Intellectual developmental disorder with autism and macrocephaly, a condition marked by impaired intellectual development and a highly penetrant autism spectrum phenotype. Understanding CHD8's role could unveil new therapeutic strategies for managing this disorder, emphasizing its significance in genetic research and drug discovery.