AI-ACCELERATED DRUG DISCOVERY

Delta(24)-sterol reductase

Explore its Potential with AI-Driven Innovation
Predicted by Alphafold

Delta(24)-sterol reductase - Focused Library Design

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(24)-sterol reductase 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(24)-sterol reductase 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(24)-sterol reductase, 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(24)-sterol reductase. 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(24)-sterol reductase. 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(24)-sterol reductase 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(24)-sterol reductase

partner:

Reaxense

upacc:

Q15392

UPID:

DHC24_HUMAN

Alternative names:

24-dehydrocholesterol reductase; 3-beta-hydroxysterol Delta-24-reductase; Diminuto/dwarf1 homolog; Seladin-1

Alternative UPACC:

Q15392; B7Z817; D3DQ51; Q9HBA8

Background:

Delta(24)-sterol reductase, also known as 24-dehydrocholesterol reductase, plays a pivotal role in cholesterol biosynthesis. It catalyzes the reduction of the delta-24 double bond of sterol intermediates, a critical step in the production of cholesterol. This enzyme not only contributes to cholesterol synthesis but also offers cellular protection against oxidative stress by reducing caspase 3 activity during apoptosis and guarding against amyloid-beta peptide-induced apoptosis.

Therapeutic significance:

Desmosterolosis, a rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of desmosterol, is directly linked to mutations affecting Delta(24)-sterol reductase. Understanding the role of Delta(24)-sterol reductase could open doors to potential therapeutic strategies for treating desmosterolosis and possibly other cholesterol-related disorders.

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