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 Calcium-transporting ATPase type 2C member 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 Calcium-transporting ATPase type 2C member 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 Calcium-transporting ATPase type 2C member 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 Calcium-transporting ATPase type 2C member 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 Calcium-transporting ATPase type 2C member 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 Calcium-transporting ATPase type 2C member 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.
Calcium-transporting ATPase type 2C member 1
partner:
Reaxense
upacc:
P98194
UPID:
AT2C1_HUMAN
Alternative names:
ATP-dependent Ca(2+) pump PMR1; Ca(2+)/Mn(2+)-ATPase 2C1; Secretory pathway Ca(2+)-transporting ATPase type 1
Alternative UPACC:
P98194; B2RAT7; B4DSW3; B7Z3X9; G3XAH8; G8JLN9; O76005; Q86V72; Q86V73; Q8N6V1; Q8NCJ7
Background:
Calcium-transporting ATPase type 2C member 1, also known as ATP-dependent Ca(2+) pump PMR1, plays a crucial role in maintaining Ca(2+) homeostasis in the trans-Golgi compartment. It functions by transporting Ca(2+) and Mn(2+) ions from the cytoplasm to the lumen of the Golgi apparatus, a process essential for the proper sorting and trafficking of newly synthesized proteins. This protein's activity is pivotal in keratinocyte differentiation, epidermis integrity, and neural polarity.
Therapeutic significance:
Mutations in this protein are linked to Hailey-Hailey disease, an autosomal dominant disorder characterized by blistering skin due to impaired keratinocyte adhesion. Understanding the role of Calcium-transporting ATPase type 2C member 1 could lead to targeted therapies for this debilitating condition.
