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 Retinal guanylyl cyclase 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 Retinal guanylyl cyclase 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 Retinal guanylyl cyclase 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 Retinal guanylyl cyclase 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 Retinal guanylyl cyclase 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 Retinal guanylyl cyclase 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.
Retinal guanylyl cyclase 1
partner:
Reaxense
upacc:
Q02846
UPID:
GUC2D_HUMAN
Alternative names:
CG-E; Guanylate cyclase 2D, retinal; Rod outer segment membrane guanylate cyclase
Alternative UPACC:
Q02846; Q6LEA7
Background:
Retinal guanylyl cyclase 1, also known as Guanylate cyclase 2D, retinal, plays a pivotal role in the phototransduction pathway by catalyzing the synthesis of cyclic GMP (cGMP) in rods and cones of photoreceptors. This enzyme is crucial for replenishing cGMP, essential for normal vision, and may also assist in the trafficking of proteins to the photoreceptor outer segment membrane.
Therapeutic significance:
Given its central role in vision, mutations in Retinal guanylyl cyclase 1 are linked to several inherited retinal dystrophies, including Leber congenital amaurosis 1, Cone-rod dystrophy 6, and others. Understanding the function and regulation of this protein could lead to novel therapeutic strategies for these blinding diseases.
