AI-ACCELERATED DRUG DISCOVERY

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2

Explore its Potential with AI-Driven Innovation
Predicted by Alphafold

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2 - Focused Library Design

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 Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 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 Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 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 Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 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 Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 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 Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 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 Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 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.

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2

partner:

Reaxense

upacc:

O95340

UPID:

PAPS2_HUMAN

Alternative names:

Sulfurylase kinase 2

Alternative UPACC:

O95340; Q9BZL2; Q9P0G6; Q9UHM1; Q9UKD3; Q9UP30

Background:

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2, also known as Sulfurylase kinase 2, plays a crucial role in the sulfate activation pathway. This enzyme mediates the transfer of sulfate to ATP, producing adenosine 5'-phosphosulfate (APS), and then transfers a phosphate group to APS, yielding 3'-phosphoadenylylsulfate (PAPS), the activated sulfate donor for sulfotransferases. Its activity is essential for providing the sole source of sulfate in mammals, highlighting its significance in biological processes.

Therapeutic significance:

The enzyme's indirect role in skeletogenesis during postnatal growth links it to Brachyolmia type 4, a skeletal dysplasia characterized by short stature and spine abnormalities. Understanding the role of Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2 could open doors to potential therapeutic strategies for treating skeletal dysplasias and improving patient outcomes.

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