C->U-editing enzyme APOBEC-1

C->U-editing enzyme APOBEC-1 - 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 C->U-editing enzyme APOBEC-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 C->U-editing enzyme APOBEC-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 C->U-editing enzyme APOBEC-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 C->U-editing enzyme APOBEC-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 C->U-editing enzyme APOBEC-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 C->U-editing enzyme APOBEC-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.

C->U-editing enzyme APOBEC-1

partner:

Reaxense

upacc:

P41238

UPID:

ABEC1_HUMAN

Alternative names:

Apolipoprotein B mRNA-editing enzyme catalytic subunit 1; HEPR; mRNA(cytosine(6666)) deaminase 1

Alternative UPACC:

P41238; Q9UE64; Q9UM71

Background:

C->U-editing enzyme APOBEC-1, also known as Apolipoprotein B mRNA-editing enzyme catalytic subunit 1, plays a pivotal role in the post-transcriptional editing of mRNAs. It catalyzes the conversion of cytidine to uridine in various mRNAs, impacting protein expression and function. This enzyme is crucial for editing the apolipoprotein B mRNA, altering a CAA codon for Gln to a UAA stop codon, and similarly edits the NF1 mRNA from CGA (Arg) to UGA (Stop). APOBEC-1's activity is modulated through complex formation with cofactors, enhancing its selectivity and editing capabilities. Additionally, it is implicated in DNA demethylation, suggesting a broader role in gene expression regulation.

Therapeutic significance:

Understanding the role of C->U-editing enzyme APOBEC-1 could open doors to potential therapeutic strategies. Its involvement in mRNA editing and gene expression regulation presents a unique opportunity for developing interventions in diseases where these processes are dysregulated.