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 Calcineurin B homologous protein 1 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 Calcineurin B homologous protein 1 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 Calcineurin B homologous protein 1, 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 Calcineurin B homologous protein 1. 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 Calcineurin B homologous protein 1. 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 Calcineurin B homologous protein 1 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.
Calcineurin B homologous protein 1
partner:
Reaxense
upacc:
Q99653
UPID:
CHP1_HUMAN
Alternative names:
Calcineurin B-like protein; Calcium-binding protein CHP; Calcium-binding protein p22; EF-hand calcium-binding domain-containing protein p22
Alternative UPACC:
Q99653; B2R6H9; Q6FHZ9
Background:
Calcineurin B homologous protein 1, also known as Calcium-binding protein CHP, plays a pivotal role in various cellular processes including vesicular trafficking, plasma membrane regulation, and gene transcription. It is essential for the association between microtubules and membrane-bound organelles, facilitating the fusion of transcytotic vesicles with the plasma membrane. Moreover, it serves as a crucial regulator of cell pH and ribosomal RNA transcription, highlighting its multifaceted function in cellular homeostasis.
Therapeutic significance:
Given its involvement in Spastic ataxia 9, an autosomal recessive disorder characterized by motor neuropathy and cerebellar atrophy, understanding the role of Calcineurin B homologous protein 1 could open doors to potential therapeutic strategies. Its regulatory function in cellular processes underscores its potential as a target for therapeutic intervention in related neurological disorders.
