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 Rac GTPase-activating protein 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 Rac GTPase-activating protein 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 Rac GTPase-activating protein 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 Rac GTPase-activating protein 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 Rac GTPase-activating protein 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 Rac GTPase-activating protein 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.
Rac GTPase-activating protein 1
partner:
Reaxense
upacc:
Q9H0H5
UPID:
RGAP1_HUMAN
Alternative names:
Male germ cell RacGap; Protein CYK4 homolog
Alternative UPACC:
Q9H0H5; Q6PJ26; Q9NWN2; Q9P250; Q9P2W2
Background:
Rac GTPase-activating protein 1, also known as Male germ cell RacGap and Protein CYK4 homolog, plays a pivotal role in cell cycle cytokinesis, erythropoiesis, and the regulation of cell growth and differentiation. It is a key component of the centralspindlin complex, essential for myosin contractile ring formation and proper attachment of the midbody during cytokinesis. Its GAP activity towards CDC42 and RAC1, and to a lesser extent RHOA, underscores its significance in various cellular processes.
Therapeutic significance:
The involvement of Rac GTPase-activating protein 1 in congenital dyserythropoietic anemia, 3B, autosomal recessive, highlights its therapeutic potential. Understanding the role of this protein could open doors to novel therapeutic strategies targeting blood disorders and possibly other conditions related to its function in cell division and differentiation.
