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 Pre-B-cell leukemia transcription factor 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 Pre-B-cell leukemia transcription factor 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 Pre-B-cell leukemia transcription factor 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 Pre-B-cell leukemia transcription factor 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 Pre-B-cell leukemia transcription factor 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 Pre-B-cell leukemia transcription factor 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.
Pre-B-cell leukemia transcription factor 1
partner:
Reaxense
upacc:
P40424
UPID:
PBX1_HUMAN
Alternative names:
Homeobox protein PBX1; Homeobox protein PRL
Alternative UPACC:
P40424; B4DSC1; F5H4U9; Q5T488
Background:
Pre-B-cell leukemia transcription factor 1 (PBX1), also known as Homeobox protein PBX1, plays a pivotal role in developmental processes. It functions as a transcription factor, binding DNA sequences to regulate gene expression in collaboration with HOX proteins and MEIS1. PBX1 is involved in various cellular processes, including the transcriptional activation of genes like PF4, SOX3, and NKX2-5, and plays a role in the development of natural killer cells and pancreatic acinar cells.
Therapeutic significance:
PBX1's involvement in congenital anomalies of the kidney and urinary tract syndrome, characterized by renal dysfunction, dysmorphic facial features, and hearing loss, underscores its therapeutic potential. Understanding the role of Pre-B-cell leukemia transcription factor 1 could open doors to potential therapeutic strategies for treating these congenital disorders.
