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 Peroxisomal ATPase PEX1 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 Peroxisomal ATPase PEX1 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 Peroxisomal ATPase PEX1, 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 Peroxisomal ATPase PEX1. 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 Peroxisomal ATPase PEX1. 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 Peroxisomal ATPase PEX1 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.
Peroxisomal ATPase PEX1
partner:
Reaxense
upacc:
O43933
UPID:
PEX1_HUMAN
Alternative names:
Peroxin-1; Peroxisome biogenesis disorder protein 1; Peroxisome biogenesis factor 1
Alternative UPACC:
O43933; A4D1G3; A8KA90; B4DIM7; E9PE75; Q96S71; Q96S72; Q96S73; Q99994
Background:
Peroxisomal ATPase PEX1, also known as Peroxin-1, plays a crucial role in the biogenesis of peroxisomes. It is part of the PEX1-PEX6 AAA ATPase complex, essential for recycling the PEX5 receptor by extracting it from peroxisomal membranes. This process is vital for the proper functioning of peroxisomes, cellular organelles that break down very long chain fatty acids and other harmful substances.
Therapeutic significance:
PEX1 is linked to a spectrum of peroxisome biogenesis disorders, including Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease. These genetic conditions underscore the protein's critical role in human health. Understanding the function of Peroxisomal ATPase PEX1 could pave the way for innovative treatments for these life-threatening disorders.
