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 Tumor protein 63 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 Tumor protein 63 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 Tumor protein 63, 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 Tumor protein 63. 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 Tumor protein 63. 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 Tumor protein 63 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.
Tumor protein 63
partner:
Reaxense
upacc:
Q9H3D4
UPID:
P63_HUMAN
Alternative names:
Chronic ulcerative stomatitis protein; Keratinocyte transcription factor KET; Transformation-related protein 63; Tumor protein p73-like; p40; p51
Alternative UPACC:
Q9H3D4; O75080; O75195; O75922; O76078; Q6VEG2; Q6VEG3; Q6VEG4; Q6VFJ1; Q6VFJ2; Q6VFJ3; Q6VH20; Q7LDI3; Q7LDI4; Q7LDI5; Q96KR0; Q9H3D2; Q9H3D3; Q9H3P8; Q9NPH7; Q9P1B4; Q9P1B5; Q9P1B6; Q9P1B7; Q9UBV9; Q9UE10; Q9UP26; Q9UP27; Q9UP28; Q9UP74
Background:
Tumor protein 63, known by various names such as p63, plays a pivotal role in epithelial development and has been implicated in a range of ectodermal dysplasia syndromes. It functions as a transcriptional activator or repressor, influencing cell cycle regulation and epithelial morphogenesis. The protein's involvement in Notch signaling and limb formation underscores its significance in cellular differentiation and tissue development.
Therapeutic significance:
Given its crucial role in ectodermal dysplasia syndromes such as Acro-dermato-ungual-lacrimal-tooth syndrome and Ankyloblepharon-ectodermal defects-cleft lip/palate, understanding the function of p63 could pave the way for innovative therapeutic approaches. Targeting the pathways regulated by p63 may offer new strategies for treating these complex disorders.
