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 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 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 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 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 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 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 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 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 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 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 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 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.
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2
partner:
Reaxense
upacc:
Q10588
UPID:
BST1_HUMAN
Alternative names:
ADP-ribosyl cyclase 2; Bone marrow stromal cell antigen 1; Cyclic ADP-ribose hydrolase 2
Alternative UPACC:
Q10588; B2R6A2; Q1XII0; Q5U0K0; Q96EN3
Background:
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2, also known as Bone marrow stromal cell antigen 1, plays a pivotal role in calcium signaling by catalyzing the synthesis and hydrolysis of cyclic ADP-beta-D-ribose (cADPR). This enzyme's activity is crucial for the mobilization of intracellular calcium, a key regulator of cellular functions and signaling pathways. Its involvement in pre-B-cell growth highlights its significance in cellular development and immune response.
Therapeutic significance:
Understanding the role of ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 could open doors to potential therapeutic strategies. Its central role in calcium signaling and immune cell development positions it as a promising target for drug discovery, aiming to modulate immune responses and treat diseases with dysregulated calcium signaling.
