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 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, 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 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, 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 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, 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 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, 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 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, 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 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, 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.
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial
partner:
Reaxense
upacc:
Q15120
UPID:
PDK3_HUMAN
Alternative names:
Pyruvate dehydrogenase kinase isoform 3
Alternative UPACC:
Q15120; B4DXG6
Background:
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial, also known as Pyruvate dehydrogenase kinase isoform 3, plays a pivotal role in regulating glucose metabolism and aerobic respiration. It achieves this by inhibiting pyruvate dehydrogenase activity through the phosphorylation of the E1 subunit PDHA1, and can also phosphorylate PDHA2. This protein is crucial in decreasing glucose utilization and increasing fat metabolism in response to prolonged fasting and adaptation to a high-fat diet. It also contributes to glucose homeostasis, maintaining normal blood glucose levels depending on nutrient levels and under starvation conditions, and is involved in the generation of reactive oxygen species.
Therapeutic significance:
Given its involvement in Charcot-Marie-Tooth disease, X-linked dominant, 6, a disorder of the peripheral nervous system characterized by progressive weakness and atrophy, understanding the role of [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial could open doors to potential therapeutic strategies targeting metabolic pathways and neurodegenerative diseases.
