Core histone macro-H2A.2

Core histone macro-H2A.2 - Focused Library Design

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 Core histone macro-H2A.2 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 Core histone macro-H2A.2 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 Core histone macro-H2A.2, 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 Core histone macro-H2A.2. 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 Core histone macro-H2A.2. 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 Core histone macro-H2A.2 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.

Core histone macro-H2A.2

partner:

Reaxense

upacc:

Q9P0M6

UPID:

H2AW_HUMAN

Alternative names:

Alternative UPACC:

Q9P0M6; Q5SQT2

Background:

Core histone macro-H2A.2, encoded by the gene with accession number Q9P0M6, plays a pivotal role in chromatin structure and function. It replaces conventional H2A in a subset of nucleosomes, leading to transcription repression. This variant histone is integral to DNA compaction, influencing transcription regulation, DNA repair, replication, and chromosomal stability. Its involvement in stable X chromosome inactivation highlights its significance in genetic regulation.

Therapeutic significance:

Understanding the role of Core histone macro-H2A.2 could open doors to potential therapeutic strategies. Its critical function in transcription regulation and chromosomal stability positions it as a key target for exploring novel treatments in genetic disorders and cancer.