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 Histone-lysine N-methyltransferase KMT5C 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 Histone-lysine N-methyltransferase KMT5C 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 Histone-lysine N-methyltransferase KMT5C, 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 Histone-lysine N-methyltransferase KMT5C. 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 Histone-lysine N-methyltransferase KMT5C. 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 Histone-lysine N-methyltransferase KMT5C 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.
Histone-lysine N-methyltransferase KMT5C
partner:
Reaxense
upacc:
Q86Y97
UPID:
KMT5C_HUMAN
Alternative names:
Lysine N-methyltransferase 5C; Lysine-specific methyltransferase 5C; Suppressor of variegation 4-20 homolog 2; [histone H4]-N-methyl-L-lysine20 N-methyltransferase KMT5B; [histone H4]-lysine20 N-methyltransferase KMT5B
Alternative UPACC:
Q86Y97; Q8WZ10; Q9BRZ6
Background:
Histone-lysine N-methyltransferase KMT5C, also known as Lysine N-methyltransferase 5C, plays a pivotal role in histone modification, specifically targeting the 'Lys-20' site on histone H4. This enzyme is crucial for the methylation process, converting monomethylated and dimethylated 'Lys-20' to dimethylated and trimethylated forms, respectively. Such modifications are essential for transcription regulation and maintaining genome integrity. KMT5C's activity is not limited to histones but extends to nucleosomes, indicating its broad role in epigenetic transcriptional repression and DNA repair mechanisms.
Therapeutic significance:
Understanding the role of Histone-lysine N-methyltransferase KMT5C could open doors to potential therapeutic strategies.
