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 Mitotic checkpoint serine/threonine-protein kinase BUB1 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 Mitotic checkpoint serine/threonine-protein kinase BUB1 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 Mitotic checkpoint serine/threonine-protein kinase BUB1, 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 Mitotic checkpoint serine/threonine-protein kinase BUB1. 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 Mitotic checkpoint serine/threonine-protein kinase BUB1. 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 Mitotic checkpoint serine/threonine-protein kinase BUB1 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.
Mitotic checkpoint serine/threonine-protein kinase BUB1
partner:
Reaxense
upacc:
O43683
UPID:
BUB1_HUMAN
Alternative names:
BUB1A
Alternative UPACC:
O43683; E9PC26; F5GXI5; O43430; O43643; O60626; Q53QE4
Background:
Mitotic checkpoint serine/threonine-protein kinase BUB1, also known as BUB1A, plays a pivotal role in mitosis. It is crucial for spindle-assembly checkpoint signaling and correct chromosome alignment, ensuring the accurate segregation of chromosomes during cell division. BUB1's kinase activity is essential for the inhibition of the anaphase-promoting complex and for chromosome alignment, highlighting its significance in maintaining genomic stability.
Therapeutic significance:
Given its critical role in cell division and genomic stability, BUB1A's dysfunction is linked to Microcephaly 30, a condition characterized by reduced brain size and developmental delays. Understanding the role of BUB1A could open doors to potential therapeutic strategies for treating microcephaly and related disorders, offering hope for patients and families affected by these conditions.
