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 Cartilage intermediate layer 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 Cartilage intermediate layer 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 Cartilage intermediate layer 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 Cartilage intermediate layer 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 Cartilage intermediate layer 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 Cartilage intermediate layer 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.
Cartilage intermediate layer protein 1
partner:
Reaxense
upacc:
O75339
UPID:
CILP1_HUMAN
Alternative names:
Cartilage intermediate-layer protein
Alternative UPACC:
O75339; B2R8F7; Q6UW99; Q8IYI5
Background:
Cartilage intermediate layer protein 1, alternatively known as Cartilage intermediate-layer protein, plays a crucial role in cartilage scaffolding. It is instrumental in modulating key growth factors, notably by antagonizing the functions of TGF-beta1 (TGFB1) and IGF1. This protein's ability to suppress IGF1-induced proliferation and sulfated proteoglycan synthesis, alongside inhibiting IGF1R autophosphorylation, underscores its regulatory significance in cartilage dynamics.
Therapeutic significance:
Given its involvement in Intervertebral disc disease, a condition marked by the degeneration of lumbar spine intervertebral disks leading to pain, the study of Cartilage intermediate layer protein 1 holds promise for novel therapeutic strategies. Its regulatory role in cartilage matrix composition and potential to influence disease progression makes it a target of interest in musculoskeletal disorder treatment.
