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 DNA-directed RNA polymerase III subunit RPC1 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 DNA-directed RNA polymerase III subunit RPC1 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 DNA-directed RNA polymerase III subunit RPC1, 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 DNA-directed RNA polymerase III subunit RPC1. 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 DNA-directed RNA polymerase III subunit RPC1. 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 DNA-directed RNA polymerase III subunit RPC1 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.
DNA-directed RNA polymerase III subunit RPC1
partner:
Reaxense
upacc:
O14802
UPID:
RPC1_HUMAN
Alternative names:
DNA-directed RNA polymerase III largest subunit; DNA-directed RNA polymerase III subunit A; RNA polymerase III 155 kDa subunit; RNA polymerase III subunit C160
Alternative UPACC:
O14802; Q8IW34; Q8TCW5
Background:
DNA-directed RNA polymerase III subunit RPC1, also known as the largest subunit of RNA polymerase III, plays a pivotal role in the transcription of DNA into RNA, utilizing ribonucleoside triphosphates as substrates. It is crucial for synthesizing small RNAs, including 5S rRNA and tRNAs, and forms the polymerase active center with the second largest subunit. This protein is also involved in the innate immune response, sensing and limiting infection by intracellular bacteria and DNA viruses by sensing non-self dsDNA.
Therapeutic significance:
The involvement of DNA-directed RNA polymerase III subunit RPC1 in Leukodystrophy, hypomyelinating, 7, and Wiedemann-Rautenstrauch syndrome, underscores its potential as a target for therapeutic intervention. Understanding the role of this protein could open doors to potential therapeutic strategies for these neurodegenerative and progeroid disorders.
