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 Xaa-Pro dipeptidase 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 Xaa-Pro dipeptidase 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 Xaa-Pro dipeptidase, 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 Xaa-Pro dipeptidase. 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 Xaa-Pro dipeptidase. 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 Xaa-Pro dipeptidase 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.
Xaa-Pro dipeptidase
partner:
Reaxense
upacc:
P12955
UPID:
PEPD_HUMAN
Alternative names:
Imidodipeptidase; Peptidase D; Proline dipeptidase
Alternative UPACC:
P12955; A8K3Z1; A8K416; A8K696; A8MX47; B4DDB7; B4DGJ1; E9PCE8; Q8TBN9; Q9BT75
Background:
Xaa-Pro dipeptidase, also known as Imidodipeptidase, Peptidase D, and Proline dipeptidase, is a crucial enzyme in collagen metabolism. It specializes in the hydrolysis of dipeptides with prolyl or hydroxyprolyl residues at the C-terminal position, favoring Gly-Pro among others. This activity is vital due to the high concentration of iminoacids in collagen, underscoring the enzyme's significant biological role.
Therapeutic significance:
Prolidase deficiency, a multisystem disorder characterized by iminodipeptiduria and reduced prolidase activity, is directly linked to mutations in the gene encoding Xaa-Pro dipeptidase. This connection highlights the enzyme's potential as a target for therapeutic intervention, aiming to alleviate the clinical manifestations such as skin ulcers, developmental delay, and recurrent infections.
