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 Epithelial splicing regulatory 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 Epithelial splicing regulatory 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 Epithelial splicing regulatory 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 Epithelial splicing regulatory 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 Epithelial splicing regulatory 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 Epithelial splicing regulatory 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.
Epithelial splicing regulatory protein 1
partner:
Reaxense
upacc:
Q6NXG1
UPID:
ESRP1_HUMAN
Alternative names:
RNA-binding motif protein 35A; RNA-binding protein 35A
Alternative UPACC:
Q6NXG1; A6NHA8; A8MPX1; E9PB47; Q2M2B0; Q499G3; Q6PJ86; Q9NXL8
Background:
Epithelial splicing regulatory protein 1, also known as RNA-binding motif protein 35A or RNA-binding protein 35A, plays a crucial role in mRNA splicing. It specifically regulates the formation of epithelial cell-specific isoforms, including FGFR2-IIIb, and is involved in the splicing of CD44, CTNND1, ENAH, crucial during the epithelial-to-mesenchymal transition. This protein's ability to bind specific sequences in mRNAs, particularly the GU-rich sequence motifs in the ISE/ISS-3 of FGFR2, underscores its significance in gene expression regulation.
Therapeutic significance:
Given its pivotal role in regulating splicing and expression of genes critical for inner ear development and auditory hair cell differentiation, Epithelial splicing regulatory protein 1 is directly linked to Deafness, autosomal recessive, 109. Understanding the role of this protein could open doors to potential therapeutic strategies for sensorineural deafness and vestibular dysplasia, offering hope for targeted interventions in genetic hearing loss conditions.
