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 85/88 kDa calcium-independent phospholipase A2 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 85/88 kDa calcium-independent phospholipase A2 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 85/88 kDa calcium-independent phospholipase A2, 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 85/88 kDa calcium-independent phospholipase A2. 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 85/88 kDa calcium-independent phospholipase A2. 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 85/88 kDa calcium-independent phospholipase A2 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.
85/88 kDa calcium-independent phospholipase A2
partner:
Reaxense
upacc:
O60733
UPID:
PLPL9_HUMAN
Alternative names:
2-lysophosphatidylcholine acylhydrolase; Group VI phospholipase A2; Intracellular membrane-associated calcium-independent phospholipase A2 beta; Palmitoyl-CoA hydrolase; Patatin-like phospholipase domain-containing protein 9
Alternative UPACC:
O60733; A8K597; B0QYE8; O75645; Q8N452; Q9UG29; Q9UIT0; Q9Y671
Background:
The 85/88 kDa calcium-independent phospholipase A2, also known as Group VI phospholipase A2, plays a crucial role in cellular processes by remodeling phospholipids, maintaining mitochondrial integrity, and participating in signal transduction. It exhibits phospholipase A1 and A2 activities, targeting various glycerophospholipids and generating lysophospholipids. This protein is involved in the repair mechanism to reduce oxidized lipid content in pancreatic beta cells and regulates membrane dynamics and homeostasis.
Therapeutic significance:
This protein's involvement in neurodegenerative disorders such as Neurodegeneration with brain iron accumulation 2A and 2B, and Parkinson disease 14, highlights its potential as a target for therapeutic intervention. Understanding the role of 85/88 kDa calcium-independent phospholipase A2 could open doors to potential therapeutic strategies for these debilitating conditions.
