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 Heat shock protein HSP 90-alpha 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 Heat shock protein HSP 90-alpha 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 Heat shock protein HSP 90-alpha, 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 Heat shock protein HSP 90-alpha. 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 Heat shock protein HSP 90-alpha. 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 Heat shock protein HSP 90-alpha 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.
Heat shock protein HSP 90-alpha
partner:
Reaxense
upacc:
P07900
UPID:
HS90A_HUMAN
Alternative names:
Heat shock 86 kDa; Lipopolysaccharide-associated protein 2; Renal carcinoma antigen NY-REN-38
Alternative UPACC:
P07900; A8K500; B3KPJ9; Q2PP14; Q5CAQ6; Q5CAQ7; Q9BVQ5
Background:
Heat shock protein HSP 90-alpha, also known as Heat shock 86 kDa, plays a pivotal role in cell cycle control and signal transduction through its molecular chaperone activity. It facilitates the maturation and structural maintenance of specific target proteins, engaging dynamically with various co-chaperones to modulate its substrate recognition and ATPase cycle. This protein is crucial in mitochondrial import, delivering preproteins to the mitochondrial import receptor TOMM70, and plays a role in the regulation of the transcription machinery and inflammatory response.
Therapeutic significance:
Understanding the role of Heat shock protein HSP 90-alpha could open doors to potential therapeutic strategies. Its involvement in cell cycle control, signal transduction, and inflammatory responses highlights its potential as a target for therapeutic intervention in diseases where these processes are dysregulated.
