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 Mothers against decapentaplegic homolog 5 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 Mothers against decapentaplegic homolog 5 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 Mothers against decapentaplegic homolog 5, 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 Mothers against decapentaplegic homolog 5. 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 Mothers against decapentaplegic homolog 5. 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 Mothers against decapentaplegic homolog 5 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.
Mothers against decapentaplegic homolog 5
partner:
Reaxense
upacc:
Q99717
UPID:
SMAD5_HUMAN
Alternative names:
JV5-1; SMAD family member 5
Alternative UPACC:
Q99717; O14688; Q15798; Q9UQA1
Background:
Mothers against decapentaplegic homolog 5 (SMAD5), also known as JV5-1, is a pivotal transcriptional regulator involved in a myriad of cellular processes such as embryonic development, cell differentiation, angiogenesis, and tissue homeostasis. It is activated upon BMP ligand binding, leading to its phosphorylation by type I BMP receptors. This activation facilitates the formation of a heteromeric complex with SMAD4, which then translocates to the nucleus to function as a transcription factor. Additionally, non-phosphorylated SMAD5 plays a crucial role in energy metabolism by promoting mitochondrial respiration and glycolysis, interacting with hexokinase 1/HK1 to accelerate glycolysis.
Therapeutic significance:
Understanding the role of Mothers against decapentaplegic homolog 5 could open doors to potential therapeutic strategies.
