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 Lysine-specific demethylase 6A 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 Lysine-specific demethylase 6A 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 Lysine-specific demethylase 6A, 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 Lysine-specific demethylase 6A. 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 Lysine-specific demethylase 6A. 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 Lysine-specific demethylase 6A 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.
Lysine-specific demethylase 6A
partner:
Reaxense
upacc:
O15550
UPID:
KDM6A_HUMAN
Alternative names:
Histone demethylase UTX; Ubiquitously-transcribed TPR protein on the X chromosome; Ubiquitously-transcribed X chromosome tetratricopeptide repeat protein; [histone H3]-trimethyl-L-lysine(27) demethylase 6A
Alternative UPACC:
O15550; Q52LL9; Q5JVQ7
Background:
Lysine-specific demethylase 6A (KDM6A), also known as Histone demethylase UTX, plays a pivotal role in epigenetic regulation by specifically demethylating 'Lys-27' of histone H3. This action is crucial for the modulation of the histone code, affecting gene expression patterns involved in posterior development and HOX gene expression. KDM6A's activity is essential for the dynamic regulation of chromatin structure, facilitating the recruitment of the PRC1 complex and influencing histone modifications.
Therapeutic significance:
KDM6A is implicated in Kabuki syndrome 2, a congenital disorder characterized by intellectual disability and distinct physical features. Understanding the role of KDM6A in this syndrome could pave the way for targeted therapeutic strategies, offering hope for patients affected by this condition.
