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 Delta(14)-sterol reductase LBR 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 Delta(14)-sterol reductase LBR 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 Delta(14)-sterol reductase LBR, 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 Delta(14)-sterol reductase LBR. 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 Delta(14)-sterol reductase LBR. 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 Delta(14)-sterol reductase LBR 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.
Delta(14)-sterol reductase LBR
partner:
Reaxense
upacc:
Q14739
UPID:
LBR_HUMAN
Alternative names:
3-beta-hydroxysterol Delta (14)-reductase; C-14 sterol reductase; Integral nuclear envelope inner membrane protein; LMN2R; Lamin-B receptor; Sterol C14-reductase
Alternative UPACC:
Q14739; B2R5P3; Q14740; Q53GU7; Q59FE6
Background:
Delta(14)-sterol reductase LBR, also known as 3-beta-hydroxysterol Delta(14)-reductase, plays a pivotal role in cholesterol biosynthesis, critical for cell growth and functional maturation in myeloid cells. It catalyzes the reduction of the C14-unsaturated bond of lanosterol, leading to cholesterol production. Additionally, it anchors the lamina and heterochromatin to the inner nuclear membrane, influencing nuclear shape and chromatin organization.
Therapeutic significance:
LBR's involvement in diseases such as Pelger-Huet anomaly, Greenberg dysplasia, Reynolds syndrome, and Rhizomelic skeletal dysplasia highlights its clinical importance. Understanding the role of Delta(14)-sterol reductase LBR could open doors to potential therapeutic strategies for these conditions, especially in targeting abnormal cholesterol biosynthesis pathways and nuclear envelope integrity.
