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 Inactive peptidyl-prolyl cis-trans isomerase FKBP6 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 Inactive peptidyl-prolyl cis-trans isomerase FKBP6 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 Inactive peptidyl-prolyl cis-trans isomerase FKBP6, 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 Inactive peptidyl-prolyl cis-trans isomerase FKBP6. 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 Inactive peptidyl-prolyl cis-trans isomerase FKBP6. 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 Inactive peptidyl-prolyl cis-trans isomerase FKBP6 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.
Inactive peptidyl-prolyl cis-trans isomerase FKBP6
partner:
Reaxense
upacc:
O75344
UPID:
FKBP6_HUMAN
Alternative names:
36 kDa FK506-binding protein; FK506-binding protein 6; Immunophilin FKBP36
Alternative UPACC:
O75344; B4DXT7; G3V0I2; Q7Z4T4; Q9UDS0
Background:
Inactive peptidyl-prolyl cis-trans isomerase FKBP6, also known as FK506-binding protein 6 or Immunophilin FKBP36, plays a pivotal role in spermatogenesis. It ensures germline integrity by repressing transposable elements through the piRNA metabolic process, forming complexes with piRNAs and Piwi proteins to mediate transposon repression. Additionally, FKBP6 acts as a co-chaperone with HSP90, crucial for piRNA amplification and secondary biogenesis.
Therapeutic significance:
Linked to Spermatogenic failure 77, a disorder marked by male infertility due to sperm abnormalities, FKBP6's understanding could pave the way for innovative treatments. Its role in maintaining germline integrity highlights its potential as a target for therapeutic strategies aimed at combating infertility issues.
