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 Forkhead box protein E3 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 Forkhead box protein E3 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 Forkhead box protein E3, 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 Forkhead box protein E3. 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 Forkhead box protein E3. 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 Forkhead box protein E3 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.
Forkhead box protein E3
partner:
Reaxense
upacc:
Q13461
UPID:
FOXE3_HUMAN
Alternative names:
Forkhead-related protein FKHL12; Forkhead-related transcription factor 8
Alternative UPACC:
Q13461; Q5SVY9; Q9NQV9
Background:
Forkhead box protein E3, also known as Forkhead-related protein FKHL12 and Forkhead-related transcription factor 8, plays a pivotal role in lens epithelial cell growth by regulating proliferation, apoptosis, and cell cycle. It is crucial for lens development, ensuring the proper ratio of lens fiber cells to anterior lens epithelium cells through its influence on cell proliferation and differentiation. Additionally, it is instrumental in lens vesicle closure and separation from the ectoderm, and controls DNAJB1 expression, vital for anterior segment eye development.
Therapeutic significance:
Given its involvement in anterior segment dysgenesis 2, cataract 34, multiple types, and familial thoracic aortic aneurysm 11, Forkhead box protein E3 represents a significant target for therapeutic intervention. Understanding its role could open doors to potential therapeutic strategies for these conditions.
