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 Transcription initiation factor IIA subunit 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 Transcription initiation factor IIA subunit 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 Transcription initiation factor IIA subunit 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 Transcription initiation factor IIA subunit 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 Transcription initiation factor IIA subunit 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 Transcription initiation factor IIA subunit 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.
Transcription initiation factor IIA subunit 2
partner:
Reaxense
upacc:
P52657
UPID:
T2AG_HUMAN
Alternative names:
General transcription factor IIA subunit 2; TFIIA p12 subunit; Transcription initiation factor IIA gamma chain
Alternative UPACC:
P52657; A8MYQ7; Q6FGB5
Background:
Transcription initiation factor IIA subunit 2 (TFIIA p12 subunit) is a pivotal component of the RNA polymerase II transcription machinery. It plays a crucial role in transcriptional activation by forming a complex with TBP, thereby mediating transcriptional activity. Known by alternative names such as General transcription factor IIA subunit 2 and Transcription initiation factor IIA gamma chain, this protein is essential for the regulation of gene expression.
Therapeutic significance:
Understanding the role of Transcription initiation factor IIA subunit 2 could open doors to potential therapeutic strategies. Its critical function in transcriptional activation positions it as a key target for research aimed at modulating gene expression in various diseases.
