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 Atrial natriuretic peptide-converting enzyme 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 Atrial natriuretic peptide-converting enzyme 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 Atrial natriuretic peptide-converting enzyme, 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 Atrial natriuretic peptide-converting enzyme. 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 Atrial natriuretic peptide-converting enzyme. 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 Atrial natriuretic peptide-converting enzyme 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.
Atrial natriuretic peptide-converting enzyme
partner:
Reaxense
upacc:
Q9Y5Q5
UPID:
CORIN_HUMAN
Alternative names:
Corin; Heart-specific serine proteinase ATC2; Pro-ANP-converting enzyme; Transmembrane protease serine 10
Alternative UPACC:
Q9Y5Q5; B0ZBE3; Q2TBD2; Q4W5E5; Q4W5G6; Q9UHY2
Background:
The Atrial natriuretic peptide-converting enzyme, known as Corin, is a serine-type endopeptidase crucial for processing natriuretic peptides such as ANP and BNP. These peptides play a pivotal role in regulating blood pressure, promoting natriuresis, diuresis, and vasodilation. Corin's activity extends to facilitating trophoblast invasion and spiral artery remodeling during pregnancy, and it also influences sodium reabsorption in the kidneys.
Therapeutic significance:
Corin's involvement in the pathophysiology of Pre-eclampsia/eclampsia 5, a hypertensive disorder of pregnancy, underscores its potential as a therapeutic target. Understanding Corin's role could pave the way for innovative treatments aimed at mitigating maternal and fetal risks associated with this condition.
