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 Ubiquitin-like modifier-activating enzyme 1 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 Ubiquitin-like modifier-activating enzyme 1 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 Ubiquitin-like modifier-activating enzyme 1, 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 Ubiquitin-like modifier-activating enzyme 1. 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 Ubiquitin-like modifier-activating enzyme 1. 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 Ubiquitin-like modifier-activating enzyme 1 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.
Ubiquitin-like modifier-activating enzyme 1
partner:
Reaxense
upacc:
P22314
UPID:
UBA1_HUMAN
Alternative names:
Protein A1S9; Ubiquitin-activating enzyme E1
Alternative UPACC:
P22314; Q5JRR8; Q96E13
Background:
Ubiquitin-like modifier-activating enzyme 1, also known as Ubiquitin-activating enzyme E1 and Protein A1S9, plays a pivotal role in the ubiquitin-proteasome system. It catalyzes the initial step in ubiquitin conjugation, marking proteins for degradation. This enzyme is crucial for DNA repair, stress response, and the formation of radiation-induced foci by promoting the recruitment of TP53BP1 and BRCA1 at DNA damage sites.
Therapeutic significance:
The enzyme's involvement in Spinal muscular atrophy X-linked 2 and VEXAS syndrome, diseases characterized by neuromuscular degeneration and inflammatory syndromes, respectively, underscores its therapeutic potential. Targeting Ubiquitin-like modifier-activating enzyme 1 could lead to innovative treatments for these conditions.
