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 DDB1- and CUL4-associated factor 15 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 DDB1- and CUL4-associated factor 15 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 DDB1- and CUL4-associated factor 15, 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 DDB1- and CUL4-associated factor 15. 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 DDB1- and CUL4-associated factor 15. 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 DDB1- and CUL4-associated factor 15 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.
DDB1- and CUL4-associated factor 15
partner:
Reaxense
upacc:
Q66K64
UPID:
DCA15_HUMAN
Alternative names:
-
Alternative UPACC:
Q66K64; B3KS86; Q96DW0; Q9BU31
Background:
DDB1- and CUL4-associated factor 15 (DCAF15) plays a pivotal role in cellular processes as a substrate-recognition component of the DCX complex. This complex, a cullin-4-RING E3 ubiquitin-protein ligase, is crucial for the ubiquitination and degradation of target proteins. DCAF15 is instrumental in regulating the effector functions of natural killer (NK) cells, potentially through the ubiquitination and degradation of cohesin subunits SMC1A and SMC3. It may also enhance the activation of antigen-presenting cells (APC) and their interaction with NK cells.
Therapeutic significance:
Understanding the role of DDB1- and CUL4-associated factor 15 could open doors to potential therapeutic strategies. Its interaction with aryl sulfonamide anticancer drugs, which alter the substrate specificity of the DCX(DCAF15) complex, underscores its therapeutic significance. These drugs promote the degradation of splicing factors like RBM39, leading to splicing defects and cancer cell death, highlighting DCAF15's potential in cancer therapy.
