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 Disks large homolog 4 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 Disks large homolog 4 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 Disks large homolog 4, 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 Disks large homolog 4. 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 Disks large homolog 4. 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 Disks large homolog 4 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.
Disks large homolog 4
partner:
Reaxense
upacc:
P78352
UPID:
DLG4_HUMAN
Alternative names:
Postsynaptic density protein 95; Synapse-associated protein 90
Alternative UPACC:
P78352; B7Z1S1; G5E939; Q92941; Q9UKK8
Background:
Disks large homolog 4 (DLG4), also known as Postsynaptic density protein 95 or Synapse-associated protein 90, is pivotal in synaptogenesis and synaptic plasticity. It facilitates the clustering of essential synaptic proteins, interacts with NMDA receptor subunits and potassium channels, and is crucial for NMDA receptor signaling-mediated synaptic plasticity. DLG4's role extends to regulating the intracellular trafficking of certain proteins and maintaining AMPA-type glutamate receptor activation at synaptic sites.
Therapeutic significance:
DLG4's mutation is linked to Intellectual developmental disorder, autosomal dominant 62, characterized by impaired intellectual development. Understanding DLG4's function could unveil novel therapeutic strategies for treating synaptic disorders and intellectual disabilities.
