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 Serine/threonine-protein kinase MRCK beta 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 Serine/threonine-protein kinase MRCK beta 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 Serine/threonine-protein kinase MRCK beta, 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 Serine/threonine-protein kinase MRCK beta. 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 Serine/threonine-protein kinase MRCK beta. 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 Serine/threonine-protein kinase MRCK beta 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.
Serine/threonine-protein kinase MRCK beta
partner:
Reaxense
upacc:
Q9Y5S2
UPID:
MRCKB_HUMAN
Alternative names:
CDC42-binding protein kinase beta; DMPK-like beta; Myotonic dystrophy kinase-related CDC42-binding kinase beta
Alternative UPACC:
Q9Y5S2; A9JR72; Q2L7A5; Q86TJ1; Q9ULU5
Background:
Serine/threonine-protein kinase MRCK beta, also known as CDC42-binding protein kinase beta, plays a pivotal role in cytoskeleton reorganization and cell migration. It achieves this through phosphorylation of key proteins such as PPP1R12C and MYL9/MLC2, crucial for actin cytoskeletal reorganization. Additionally, it collaborates with MYO18A and LURAP1 to modulate lamellar actomyosin retrograde flow, essential for cell protrusion and migration.
Therapeutic significance:
The protein's involvement in Chilton-Okur-Chung neurodevelopmental syndrome, characterized by developmental delay and intellectual disability, underscores its therapeutic significance. Understanding the role of Serine/threonine-protein kinase MRCK beta could open doors to potential therapeutic strategies for this and related disorders.
