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 Glutamate carboxypeptidase 2 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 Glutamate carboxypeptidase 2 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 Glutamate carboxypeptidase 2, 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 Glutamate carboxypeptidase 2. 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 Glutamate carboxypeptidase 2. 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 Glutamate carboxypeptidase 2 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.
Glutamate carboxypeptidase 2
partner:
Reaxense
upacc:
Q04609
UPID:
FOLH1_HUMAN
Alternative names:
Cell growth-inhibiting gene 27 protein; Folate hydrolase 1; Folylpoly-gamma-glutamate carboxypeptidase; Glutamate carboxypeptidase II; Membrane glutamate carboxypeptidase; N-acetylated-alpha-linked acidic dipeptidase I; Prostate-specific membrane antigen; Pteroylpoly-gamma-glutamate carboxypeptidase
Alternative UPACC:
Q04609; A4UU12; A9CB79; B7Z312; B7Z343; D3DQS5; E9PDX8; O43748; Q16305; Q541A4; Q8TAY3; Q9NP15; Q9NYE2; Q9P1P8
Background:
Glutamate carboxypeptidase 2 (GCPII) is a multifunctional protein with critical roles in various biological processes, including folate absorption and neurotransmission modulation. Known by several names such as Folate hydrolase 1 and Prostate-specific membrane antigen, it exhibits folate hydrolase and NAALADase activity, crucial for folate uptake in the intestine and modulating excitatory neurotransmission in the brain by hydrolyzing NAAG.
Therapeutic significance:
Understanding the role of Glutamate carboxypeptidase 2 could open doors to potential therapeutic strategies. Its involvement in modulating neurotransmission and folate uptake presents a unique opportunity for developing treatments targeting neurological conditions and enhancing nutrient absorption.
