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 Protein diaphanous homolog 3 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 Protein diaphanous homolog 3 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 Protein diaphanous homolog 3, 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 Protein diaphanous homolog 3. 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 Protein diaphanous homolog 3. 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 Protein diaphanous homolog 3 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.
Protein diaphanous homolog 3
partner:
Reaxense
upacc:
Q9NSV4
UPID:
DIAP3_HUMAN
Alternative names:
Diaphanous-related formin-3; MDia2
Alternative UPACC:
Q9NSV4; A2A3B8; A2A3B9; A2A3C0; Q18P99; Q18PA0; Q18PA1; Q2KPB6; Q3ZK23; Q5JTP8; Q5T2S7; Q5XKF6; Q6MZF0; Q6NUP0; Q86VS4; Q8NAV4
Background:
Protein diaphanous homolog 3, also known as Diaphanous-related formin-3 or MDia2, plays a pivotal role in actin nucleation and elongation. It is essential for the assembly of F-actin structures, such as actin cables and stress fibers, and is crucial for processes like cytokinesis and stress fiber formation. MDia2 functions by binding to the GTP-bound form of Rho and to profilin, facilitating actin polymerization in a Rho-dependent manner. Its activity is integral to the coupling of Rho and Src tyrosine kinase signaling and the regulation of actin dynamics, including in the nucleus to drive serum-dependent SRF-MRTFA activity.
Therapeutic significance:
MDia2's involvement in auditory neuropathy, autosomal dominant 1, highlights its potential as a target for therapeutic intervention. This condition, characterized by sensorineural hearing loss and abnormal auditory brainstem response, underscores the critical role of MDia2 in auditory pathways. Understanding the role of Protein diaphanous homolog 3 could open doors to potential therapeutic strategies.
