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 Ribosomal RNA small subunit methyltransferase NEP1 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 Ribosomal RNA small subunit methyltransferase NEP1 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 Ribosomal RNA small subunit methyltransferase NEP1, 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 Ribosomal RNA small subunit methyltransferase NEP1. 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 Ribosomal RNA small subunit methyltransferase NEP1. 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 Ribosomal RNA small subunit methyltransferase NEP1 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.
Ribosomal RNA small subunit methyltransferase NEP1
partner:
Reaxense
upacc:
Q92979
UPID:
NEP1_HUMAN
Alternative names:
18S rRNA (pseudouridine(1248)-N1)-methyltransferase; 18S rRNA Psi1248 methyltransferase; Nucleolar protein EMG1 homolog; Protein C2f; Ribosome biogenesis protein NEP1
Alternative UPACC:
Q92979; O00675; O00726
Background:
Ribosomal RNA small subunit methyltransferase NEP1, also known as 18S rRNA Psi1248 methyltransferase, plays a pivotal role in ribosome biogenesis. It is a S-adenosyl-L-methionine-dependent enzyme that specifically methylates pseudouridine at position 1248 in 18S rRNA, a modification crucial for the production of the hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine. This protein is integral to the small subunit (SSU) processome, facilitating the assembly of ribosomal protein S19 and ensuring the proper formation of pre-ribosomes.
Therapeutic significance:
The association of Ribosomal RNA small subunit methyltransferase NEP1 with Bowen-Conradi syndrome, a condition marked by severe developmental anomalies and early infant mortality, underscores its clinical importance. Understanding the role of this protein could open doors to potential therapeutic strategies aimed at mitigating the effects of this syndrome.
