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 DDRGK domain-containing 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 DDRGK domain-containing 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 DDRGK domain-containing 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 DDRGK domain-containing 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 DDRGK domain-containing 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 DDRGK domain-containing 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.
DDRGK domain-containing protein 1
partner:
Reaxense
upacc:
Q96HY6
UPID:
DDRGK_HUMAN
Alternative names:
Dashurin; UFM1-binding and PCI domain-containing protein 1
Alternative UPACC:
Q96HY6; A6NIU5; C9JSZ5; Q9BW47
Background:
DDRGK domain-containing protein 1, also known as Dashurin, plays a pivotal role in cellular processes, including reticulophagy, by acting as a substrate adapter for ufmylation. This protein is essential in responding to endoplasmic reticulum stress, facilitating the recruitment of the E3 UFM1-protein ligase UFL1, and promoting the ufmylation of proteins such as RPN1 and RPL26/uL24. Its involvement in regulating the unfolded protein response and essential processes like hematopoiesis and the inflammatory response underscores its biological significance.
Therapeutic significance:
DDRGK domain-containing protein 1's link to Spondyloepimetaphyseal dysplasia, Shohat type, a skeletal dysplasia affecting cartilage development, highlights its therapeutic potential. Understanding its role could lead to novel therapeutic strategies targeting skeletal dysplasias and other related disorders.
