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 Krev interaction trapped protein 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 Krev interaction trapped protein 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 Krev interaction trapped protein 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 Krev interaction trapped protein 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 Krev interaction trapped protein 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 Krev interaction trapped protein 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.
Krev interaction trapped protein 1
partner:
Reaxense
upacc:
O00522
UPID:
KRIT1_HUMAN
Alternative names:
Cerebral cavernous malformations 1 protein
Alternative UPACC:
O00522; A6NNU0; O43894; Q506L6; Q6U276; Q75N19; Q9H180; Q9H264; Q9HAX5
Background:
Krev interaction trapped protein 1, also known as Cerebral cavernous malformations 1 protein, plays a pivotal role in the CCM signaling pathway, crucial for heart and vessel formation and integrity. It acts as a negative regulator of angiogenesis, influencing endothelial proliferation, apoptosis, migration, and sprouting angiogenesis. The protein is involved in various signaling cascades, including AKT phosphorylation and the DELTA-NOTCH cascade, contributing to vascular lumen stability and endothelial cell polarity.
Therapeutic significance:
Given its central role in cerebral cavernous malformations 1, a condition leading to hemorrhagic stroke and seizures, Krev interaction trapped protein 1 presents a promising target for therapeutic intervention. Understanding its function could pave the way for novel treatments aimed at mitigating the vascular anomalies associated with this disease.
