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 Lymphoid-specific helicase 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 Lymphoid-specific helicase 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 Lymphoid-specific helicase, 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 Lymphoid-specific helicase. 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 Lymphoid-specific helicase. 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 Lymphoid-specific helicase 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.
Lymphoid-specific helicase
partner:
Reaxense
upacc:
Q9NRZ9
UPID:
HELLS_HUMAN
Alternative names:
Proliferation-associated SNF2-like protein; SWI/SNF2-related matrix-associated actin-dependent regulator of chromatin subfamily A member 6
Alternative UPACC:
Q9NRZ9; B2RB41; Q3LID1; Q6I7N7; Q76H76; Q76H77; Q76H78; Q76H79; Q76H80; Q76H81; Q7Z397; Q7Z5X2; Q8N6P4; Q9H4P5
Background:
The Lymphoid-specific helicase, also known as Proliferation-associated SNF2-like protein or SWI/SNF2-related matrix-associated actin-dependent regulator of chromatin subfamily A member 6, plays a pivotal role in development and survival. It is crucial for DNA methylation, a process essential for the regulation of gene expression and maintenance of genomic integrity. This protein is also involved in lymphoid cell expansion and may influence heterochromatin formation, impacting transcription and mitosis.
Therapeutic significance:
Given its essential role in DNA methylation and lymphoid cell regulation, the Lymphoid-specific helicase is linked to Immunodeficiency-centromeric instability-facial anomalies syndrome 4, a rare disorder with immunodeficiency and genomic instability. Understanding the role of this protein could open doors to potential therapeutic strategies for this syndrome and related conditions.
