Ribonucleases P/MRP protein subunit POP1

Ribonucleases P/MRP protein subunit POP1 - 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 Ribonucleases P/MRP protein subunit POP1 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 Ribonucleases P/MRP protein subunit POP1 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 Ribonucleases P/MRP protein subunit POP1, 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 Ribonucleases P/MRP protein subunit POP1. 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 Ribonucleases P/MRP protein subunit POP1. 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 Ribonucleases P/MRP protein subunit POP1 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.

Ribonucleases P/MRP protein subunit POP1

partner:

Reaxense

upacc:

Q99575

UPID:

POP1_HUMAN

Alternative names:

Alternative UPACC:

Q99575; A8K5W9; Q15037

Background:

The Ribonucleases P/MRP protein subunit POP1 plays a crucial role in cellular function, being a key component of ribonuclease P and the MRP ribonuclease complex. These complexes are essential for generating mature tRNA molecules and cleaving pre-rRNA sequences, respectively, highlighting the protein's pivotal role in RNA processing.

Therapeutic significance:

Given its involvement in Anauxetic dysplasia 2, a condition marked by severe short stature and mild intellectual disability, targeting POP1 could offer novel therapeutic avenues. Understanding the role of Ribonucleases P/MRP protein subunit POP1 could open doors to potential therapeutic strategies.