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 N-alpha-acetyltransferase 10 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 N-alpha-acetyltransferase 10 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 N-alpha-acetyltransferase 10, 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 N-alpha-acetyltransferase 10. 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 N-alpha-acetyltransferase 10. 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 N-alpha-acetyltransferase 10 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.
N-alpha-acetyltransferase 10
partner:
Reaxense
upacc:
P41227
UPID:
NAA10_HUMAN
Alternative names:
N-terminal acetyltransferase complex ARD1 subunit homolog A; NatA catalytic subunit Naa10
Alternative UPACC:
P41227; A6NM98
Background:
N-alpha-acetyltransferase 10, known as Naa10, plays a pivotal role in protein synthesis and function. It acts as the catalytic subunit of N-terminal acetyltransferase complexes, modifying proteins by acetylating their amino termini. This modification is crucial for various biological processes, including vascular, hematopoietic, and neuronal growth and development. Naa10's ability to acetylate and stabilize key proteins like TSC2 and HSPA1A enhances its significance in cellular homeostasis and stress response.
Therapeutic significance:
Naa10's involvement in diseases such as N-terminal acetyltransferase deficiency and Microphthalmia, syndromic, 1, underscores its therapeutic potential. By understanding Naa10's role in these conditions, researchers can develop targeted therapies to modulate its activity. This could lead to innovative treatments for these genetic disorders, offering hope for affected individuals.
