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 Poly(A)-specific ribonuclease PNLDC1 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 Poly(A)-specific ribonuclease PNLDC1 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 Poly(A)-specific ribonuclease PNLDC1, 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 Poly(A)-specific ribonuclease PNLDC1. 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 Poly(A)-specific ribonuclease PNLDC1. 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 Poly(A)-specific ribonuclease PNLDC1 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.
Poly(A)-specific ribonuclease PNLDC1
partner:
Reaxense
upacc:
Q8NA58
UPID:
PNDC1_HUMAN
Alternative names:
PARN-like domain-containing protein 1; Poly(A)-specific ribonuclease domain-containing protein 1
Alternative UPACC:
Q8NA58; Q5TAP7; Q8N7X5
Background:
Poly(A)-specific ribonuclease PNLDC1, also known as PARN-like domain-containing protein 1, plays a pivotal role in mRNA decay by degrading poly(A) tails. This process is crucial for the regulation of gene expression in eukaryotic cells, including during oocyte maturation and early embryonic development. PNLDC1's activity is essential for maintaining the balance of stem cell multipotency and is a key player in spermatogenesis, facilitating the processing of pre-piRNAs into mature piRNAs.
Therapeutic significance:
PNLDC1's critical function in spermatogenesis links it to Spermatogenic failure 57, a condition marked by non-obstructive azoospermia. Understanding PNLDC1's role could lead to novel treatments for male infertility, highlighting its potential as a target in therapeutic strategies aimed at restoring fertility.
