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 Bis(5'-adenosyl)-triphosphatase 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 Bis(5'-adenosyl)-triphosphatase 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 Bis(5'-adenosyl)-triphosphatase, 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 Bis(5'-adenosyl)-triphosphatase. 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 Bis(5'-adenosyl)-triphosphatase. 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 Bis(5'-adenosyl)-triphosphatase 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.
Bis(5'-adenosyl)-triphosphatase
partner:
Reaxense
upacc:
P49789
UPID:
FHIT_HUMAN
Alternative names:
AP3A hydrolase; Adenosine 5'-monophosphoramidase FHIT; Adenylylsulfatase; Adenylylsulfate-ammonia adenylyltransferase; Diadenosine 5',5'''-P1,P3-triphosphate hydrolase; Dinucleosidetriphosphatase; Fragile histidine triad protein
Alternative UPACC:
P49789; A2IAS9; A2IAT0; A2IAT6; A8K1A9; Q45QG9; Q6IU12
Background:
The Bis(5'-adenosyl)-triphosphatase, known by its alternative names such as AP3A hydrolase and Fragile histidine triad protein, exhibits a broad spectrum of enzymatic activities. It is capable of hydrolyzing dinucleoside triphosphates like Ap3A into AMP and ADP, and possesses adenylylsulfatase activity, converting adenosine 5'-phosphosulfate into AMP and sulfate. Furthermore, it plays a crucial role in modulating transcriptional activation by CTNNB1, influencing cell proliferation and survival through the regulation of genes like CCND1 and BIRC5. Its involvement in apoptosis through SRC and AKT1 signaling pathways, and its ability to inhibit MDM2-mediated degradation of p53/TP53, highlight its significance in cellular processes.
Therapeutic significance:
Understanding the role of Bis(5'-adenosyl)-triphosphatase could open doors to potential therapeutic strategies.
