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 U5 small nuclear ribonucleoprotein 200 kDa helicase 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 U5 small nuclear ribonucleoprotein 200 kDa helicase 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 U5 small nuclear ribonucleoprotein 200 kDa helicase, 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 U5 small nuclear ribonucleoprotein 200 kDa helicase. 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 U5 small nuclear ribonucleoprotein 200 kDa helicase. 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 U5 small nuclear ribonucleoprotein 200 kDa helicase 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.
U5 small nuclear ribonucleoprotein 200 kDa helicase
partner:
Reaxense
upacc:
O75643
UPID:
U520_HUMAN
Alternative names:
Activating signal cointegrator 1 complex subunit 3-like 1; BRR2 homolog; U5 snRNP-specific 200 kDa protein
Alternative UPACC:
O75643; O94884; Q6NZY0; Q6PX59; Q8NBE6; Q96IF2; Q9H7S0
Background:
The U5 small nuclear ribonucleoprotein 200 kDa helicase, also known as Activating signal cointegrator 1 complex subunit 3-like 1, BRR2 homolog, and U5 snRNP-specific 200 kDa protein, plays a pivotal role in pre-mRNA splicing. It catalyzes the ATP-dependent unwinding of U4/U6 RNA duplexes, a crucial step in spliceosome assembly, activation, and disassembly. This protein is a core component of precatalytic, catalytic, and postcatalytic spliceosomal complexes, involved in the dynamic network of RNA-RNA interactions.
Therapeutic significance:
Given its essential role in pre-mRNA splicing and association with Retinitis pigmentosa 33, understanding the function of U5 small nuclear ribonucleoprotein 200 kDa helicase could unveil novel therapeutic strategies for treating this retinal dystrophy. Targeting the spliceosomal machinery offers a promising avenue for drug discovery in genetic disorders.
