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 60 kDa heat shock protein, mitochondrial 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 60 kDa heat shock protein, mitochondrial 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 60 kDa heat shock protein, mitochondrial, 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 60 kDa heat shock protein, mitochondrial. 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 60 kDa heat shock protein, mitochondrial. 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 60 kDa heat shock protein, mitochondrial 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.
60 kDa heat shock protein, mitochondrial
partner:
Reaxense
upacc:
P10809
UPID:
CH60_HUMAN
Alternative names:
60 kDa chaperonin; Chaperonin 60; Heat shock protein 60; HuCHA60; Mitochondrial matrix protein P1; P60 lymphocyte protein
Alternative UPACC:
P10809; B2R5M6; B7Z712; Q38L19; Q9UCR6
Background:
The 60 kDa heat shock protein, mitochondrial (Hsp60), plays a pivotal role in mitochondrial protein import and macromolecular assembly. It works in tandem with Hsp10 to ensure the correct folding of imported proteins and to assist in the refolding of stress-generated unfolded polypeptides in the mitochondrial matrix. Hsp60's function is crucial for maintaining cellular function under stress conditions, highlighting its importance in cellular homeostasis.
Therapeutic significance:
Hsp60 is implicated in diseases such as Spastic paraplegia 13, autosomal dominant, and Leukodystrophy, hypomyelinating, 4, both of which involve neurodegenerative processes. Understanding the role of Hsp60 could open doors to potential therapeutic strategies for these and other mitochondrial dysfunction-related diseases.
