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 Leukotriene C4 synthase 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 Leukotriene C4 synthase 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 Leukotriene C4 synthase, 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 Leukotriene C4 synthase. 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 Leukotriene C4 synthase. 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 Leukotriene C4 synthase 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.
Leukotriene C4 synthase
partner:
Reaxense
upacc:
Q16873
UPID:
LTC4S_HUMAN
Alternative names:
Glutathione S-transferase LTC4; Leukotriene-C(4) synthase; Leukotriene-C4 synthase
Alternative UPACC:
Q16873; Q8N6P0; Q9UC73; Q9UD18
Background:
Leukotriene C4 synthase, also known as Glutathione S-transferase LTC4, plays a pivotal role in the biosynthesis of leukotriene C4 from leukotriene A4 and glutathione. This enzyme exhibits high specificity in its catalytic activity, as evidenced by its ability to also catalyze the formation of maresin conjugate in tissue regeneration 1 (MCTR1), a lipid mediator with significant anti-inflammatory and proresolving properties.
Therapeutic significance:
Understanding the role of Leukotriene C4 synthase could open doors to potential therapeutic strategies. Its involvement in the production of bioactive lipid mediators highlights its potential as a target for developing treatments aimed at modulating inflammatory responses and facilitating tissue regeneration.
