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 Endoplasmic reticulum chaperone BiP 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 Endoplasmic reticulum chaperone BiP 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 Endoplasmic reticulum chaperone BiP, 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 Endoplasmic reticulum chaperone BiP. 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 Endoplasmic reticulum chaperone BiP. 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 Endoplasmic reticulum chaperone BiP 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.
Endoplasmic reticulum chaperone BiP
partner:
Reaxense
upacc:
P11021
UPID:
BIP_HUMAN
Alternative names:
78 kDa glucose-regulated protein; Binding-immunoglobulin protein; Heat shock protein 70 family protein 5; Heat shock protein family A member 5; Immunoglobulin heavy chain-binding protein
Alternative UPACC:
P11021; B0QZ61; Q2EF78; Q9NPF1; Q9UK02
Background:
The Endoplasmic reticulum chaperone BiP, also known as the 78 kDa glucose-regulated protein, plays a crucial role in protein folding and quality control within the endoplasmic reticulum. It is essential for the correct folding of proteins and the degradation of misfolded proteins, acting through its interaction with DNAJC10/ERdj5. BiP is a key repressor of the ERN1/IRE1-mediated unfolded protein response, a vital process in cellular stress management.
Therapeutic significance:
Understanding the role of Endoplasmic reticulum chaperone BiP could open doors to potential therapeutic strategies. Its involvement in protein folding and stress responses in the endoplasmic reticulum highlights its potential as a target in diseases related to protein misfolding and cellular stress.
