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 N-terminal Xaa-Pro-Lys N-methyltransferase 2 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 N-terminal Xaa-Pro-Lys N-methyltransferase 2 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 N-terminal Xaa-Pro-Lys N-methyltransferase 2, 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 N-terminal Xaa-Pro-Lys N-methyltransferase 2. 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 N-terminal Xaa-Pro-Lys N-methyltransferase 2. 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 N-terminal Xaa-Pro-Lys N-methyltransferase 2 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.
N-terminal Xaa-Pro-Lys N-methyltransferase 2
partner:
Reaxense
upacc:
Q5VVY1
UPID:
NTM1B_HUMAN
Alternative names:
Alpha N-terminal protein methyltransferase 1B; Methyltransferase-like protein 11B; X-Pro-Lys N-terminal protein methyltransferase 1B
Alternative UPACC:
Q5VVY1; B2RXI0
Background:
N-terminal Xaa-Pro-Lys N-methyltransferase 2, also known as Alpha N-terminal protein methyltransferase 1B, plays a crucial role in post-translational modification. It specifically catalyzes the monomethylation of the alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif, a process vital for protein function and regulation. This enzyme's activity is pivotal in modifying proteins after the initial synthesis, impacting their stability, localization, and interaction with other molecules.
Therapeutic significance:
Understanding the role of N-terminal Xaa-Pro-Lys N-methyltransferase 2 could open doors to potential therapeutic strategies. Its unique function in protein modification underscores its importance in cellular processes and disease mechanisms, making it a compelling target for drug discovery efforts.
