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 Choline transporter-like protein 4 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 Choline transporter-like protein 4 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 Choline transporter-like protein 4, 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 Choline transporter-like protein 4. 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 Choline transporter-like protein 4. 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 Choline transporter-like protein 4 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.
Choline transporter-like protein 4
partner:
Reaxense
upacc:
Q53GD3
UPID:
CTL4_HUMAN
Alternative names:
Solute carrier family 44 member 4; Thiamine pyrophosphate transporter 1
Alternative UPACC:
Q53GD3; A2BED3; B0UXX8; B0UZY8; B4DU94; B4DWM2; E9PEK7; Q5JP84; Q5JQ93; Q658S8; Q6UX89; Q8TEW4; Q96C58; Q96K59; Q9Y332
Background:
Choline transporter-like protein 4, also known as Solute carrier family 44 member 4 and Thiamine pyrophosphate transporter 1, plays a crucial role in the choline-acetylcholine system. It is essential for the efferent innervation of hair cells in the olivocochlear bundle, maintaining the physiological function of outer hair cells and protecting them from acoustic injury. Additionally, it functions as a thiamine pyrophosphate transporter in the colon, contributing to host thiamine homeostasis.
Therapeutic significance:
The protein's involvement in Deafness, autosomal dominant, 72, a form of non-syndromic sensorineural hearing loss affecting middle frequencies, highlights its potential as a target for therapeutic intervention. Understanding the role of Choline transporter-like protein 4 could open doors to novel treatments for hearing loss and thiamine deficiency disorders.
