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 IST1 homolog 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 IST1 homolog 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 IST1 homolog, 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 IST1 homolog. 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 IST1 homolog. 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 IST1 homolog 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.
IST1 homolog
partner:
Reaxense
upacc:
P53990
UPID:
IST1_HUMAN
Alternative names:
Charged multivesicular body protein 8; Putative MAPK-activating protein PM28
Alternative UPACC:
P53990; A8KAH5; J3QLU7; Q3SYM4; Q9BQ81; Q9BWN2
Background:
IST1 homolog, also known as Charged multivesicular body protein 8 and Putative MAPK-activating protein PM28, plays a pivotal role in cellular processes such as cytokinesis, nuclear envelope reassembly, and endosomal tubulation. It is essential for efficient abscission during cytokinesis by recruiting VPS4A and/or VPS4B to the midbody of dividing cells. Furthermore, IST1 is involved in nuclear envelope reassembly and mitotic spindle disassembly by mediating the recruitment of SPAST to the nuclear membrane. It also regulates early endosomal tubulation by collaborating with the ESCRT-III complex.
Therapeutic significance:
Understanding the role of IST1 homolog could open doors to potential therapeutic strategies.
