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 43 kDa receptor-associated protein of the synapse 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 43 kDa receptor-associated protein of the synapse 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 43 kDa receptor-associated protein of the synapse, 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 43 kDa receptor-associated protein of the synapse. 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 43 kDa receptor-associated protein of the synapse. 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 43 kDa receptor-associated protein of the synapse 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.
43 kDa receptor-associated protein of the synapse
partner:
Reaxense
upacc:
Q13702
UPID:
RAPSN_HUMAN
Alternative names:
43 kDa postsynaptic protein; Acetylcholine receptor-associated 43 kDa protein; RING finger protein 205
Alternative UPACC:
Q13702; Q8TDF3; Q9BTD9
Background:
The 43 kDa receptor-associated protein of the synapse plays a pivotal role in neuromuscular junctions, specifically in the clustering of nicotinic acetylcholine receptors (nAChRs). This postsynaptic protein, also known as Acetylcholine receptor-associated 43 kDa protein and RING finger protein 205, is essential for linking the receptor to the cytoskeleton, facilitating synaptic transmission.
Therapeutic significance:
Linked to congenital myasthenic syndrome 11 and fetal akinesia deformation sequence 2, this protein's dysfunction underscores its critical role in neuromuscular diseases. Understanding its function and the genetic variants affecting it could lead to targeted therapies for these debilitating conditions.
