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 Small ribosomal subunit protein uS2 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 Small ribosomal subunit protein uS2 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 Small ribosomal subunit protein uS2, 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 Small ribosomal subunit protein uS2. 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 Small ribosomal subunit protein uS2. 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 Small ribosomal subunit protein uS2 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.
Small ribosomal subunit protein uS2
partner:
Reaxense
upacc:
P08865
UPID:
RSSA_HUMAN
Alternative names:
37 kDa laminin receptor precursor; 37/67 kDa laminin receptor; 40S ribosomal protein SA; 67 kDa laminin receptor; Colon carcinoma laminin-binding protein; Laminin receptor 1; Laminin-binding protein precursor p40; Multidrug resistance-associated protein MGr1-Ag; NEM/1CHD4
Alternative UPACC:
P08865; P11085; P12030; Q16471; Q6IPD1; Q6IPD2; Q6NSD1; Q6NXQ8; Q86VC0
Background:
Small ribosomal subunit protein uS2, known as the 40S ribosomal protein SA, plays a crucial role in the assembly and stability of the 40S ribosomal subunit. It is essential for processing the 20S rRNA-precursor into mature 18S rRNA, a key step in ribosomal subunit maturation. Additionally, it serves as a cell surface receptor for laminin, influencing cell adhesion, signaling pathways, and tissue morphogenesis. Its interaction with various pathogens, including Adeno-associated viruses, Dengue virus, and the pathogenic prion protein, highlights its significance in microbial infection.
Therapeutic significance:
Given its involvement in isolated congenital asplenia, a rare and life-threatening condition, understanding the role of Small ribosomal subunit protein uS2 could open doors to potential therapeutic strategies. Its pivotal role in ribosomal function and cell surface interactions makes it a target for addressing severe bacterial infections and possibly influencing tissue morphogenesis and disease outcomes.
