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 Prolyl endopeptidase FAP 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 Prolyl endopeptidase FAP 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 Prolyl endopeptidase FAP, 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 Prolyl endopeptidase FAP. 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 Prolyl endopeptidase FAP. 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 Prolyl endopeptidase FAP 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.
Prolyl endopeptidase FAP
partner:
Reaxense
upacc:
Q12884
UPID:
SEPR_HUMAN
Alternative names:
170 kDa melanoma membrane-bound gelatinase; Dipeptidyl peptidase FAP; Fibroblast activation protein alpha; Gelatine degradation protease FAP; Integral membrane serine protease; Post-proline cleaving enzyme; Serine integral membrane protease; Surface-expressed protease
Alternative UPACC:
Q12884; O00199; Q53TP5; Q86Z29; Q99998; Q9UID4
Background:
Prolyl endopeptidase FAP, a cell surface glycoprotein serine protease, plays a pivotal role in extracellular matrix degradation. It is involved in various cellular processes such as tissue remodeling, fibrosis, wound healing, inflammation, and tumor growth. This enzyme exhibits a preference for specific consensus sequences and degrades multiple substrates including gelatin and heat-denatured collagen, but not native collagen types I and IV. It also possesses dipeptidyl peptidase activity, targeting neuropeptide hormones.
Therapeutic significance:
Understanding the role of Prolyl endopeptidase FAP could open doors to potential therapeutic strategies. Its involvement in tissue remodeling, wound healing, and tumor progression highlights its significance in developing treatments for fibrosis, chronic wounds, and cancer. Targeting this protease could lead to innovative therapies that modulate its activity for beneficial outcomes.
