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 cGMP-dependent protein kinase 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 cGMP-dependent protein kinase 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 cGMP-dependent protein kinase 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 cGMP-dependent protein kinase 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 cGMP-dependent protein kinase 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 cGMP-dependent protein kinase 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.
cGMP-dependent protein kinase 1
partner:
Reaxense
upacc:
Q13976
UPID:
KGP1_HUMAN
Alternative names:
cGMP-dependent protein kinase I
Alternative UPACC:
Q13976; A5YM56; B3KSF3; E2PU10; P14619; Q5JP05; Q5JSJ6; Q6P5T7
Background:
cGMP-dependent protein kinase 1 (cGMP-dependent protein kinase I) plays a pivotal role in the nitric oxide (NO)/cGMP signaling pathway. It is activated by GMP binding, leading to the phosphorylation of various proteins that influence cellular processes including smooth muscle contraction, platelet activation, cardiac function, and gene expression. This kinase is crucial in regulating intracellular calcium levels and smooth muscle relaxation through multiple pathways.
Therapeutic significance:
The involvement of cGMP-dependent protein kinase 1 in familial thoracic aortic aneurysm 8 highlights its potential as a therapeutic target. Understanding the role of this protein could open doors to potential therapeutic strategies for treating cardiovascular diseases characterized by alterations in smooth muscle function and vascular integrity.
