Focused On-demand Library for Arginine-hydroxylase NDUFAF5, mitochondrial

Focused On-demand Libraries - Reaxense Collaboration

Explore the Potential with AI-Driven Innovation

The specialised, focused library is developed on demand with the most recent virtual screening and parameter assessment technology, guided by the Receptor.AI drug discovery platform. This approach exceeds the capabilities of traditional methods and offers compounds with higher activity, selectivity, and safety.

From a virtual chemical space containing more than 60 billion molecules, we precisely choose certain compounds. Our collaborator, Reaxense, aids in their synthesis and provision.

In the library, a selection of top modulators is provided, each marked with 38 ADME-Tox and 32 parameters related to physicochemical properties and drug-likeness. Also, every compound comes with its best docking poses, affinity scores, and activity scores, providing a comprehensive overview.

We employ our advanced, specialised process to create targeted libraries for enzymes.

Fig. 1. The sreening workflow of Receptor.AI

It includes comprehensive molecular simulations of the catalytic and allosteric binding pockets and the ensemble virtual screening accounting for their conformational mobility. In the case of designing modulators, the structural changes induced by reaction intermediates are taken into account to leverage activity and selectivity.

Our library is unique due to several crucial aspects:

Receptor.AI compiles all relevant data on the target protein, such as past experimental results, literature findings, known ligands, and structural data, thereby enhancing the likelihood of focusing on the most significant compounds.
By utilizing advanced molecular simulations, the platform is adept at locating potential binding sites, rendering the compounds in the focused library well-suited for unearthing allosteric inhibitors and binders for hidden pockets.
The platform is supported by more than 50 highly specialized AI models, all of which have been rigorously tested and validated in diverse drug discovery and research programs. Its design emphasizes efficiency, reliability, and accuracy, crucial for producing focused libraries.
Receptor.AI extends beyond just creating focused libraries; it offers a complete spectrum of services and solutions during the preclinical drug discovery phase, with a success-dependent pricing strategy that reduces risk and fosters shared success in the project.

partner

Reaxense

upacc

Q5TEU4

UPID:

NDUF5_HUMAN

Alternative names:

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 5; Putative methyltransferase NDUFAF5

Alternative UPACC:

Q5TEU4; A8K166; Q6GPH3; Q9H6F4

Background:

Arginine-hydroxylase NDUFAF5, mitochondrial, also known as NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 5, plays a crucial role in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1). It functions early in the assembly process, specifically mediating the hydroxylation of 'Arg-111' of NDUFS7, which is essential for complex I assembly. This protein may also exhibit methyltransferase activity.

Therapeutic significance:

Mitochondrial complex I deficiency, nuclear type 16, a condition linked to variants affecting the NDUFAF5 gene, highlights the protein's critical role in mitochondrial disorders. These disorders range from lethal neonatal diseases to adult-onset neurodegenerative disorders, including Leigh syndrome and some forms of Parkinson disease. Understanding the role of Arginine-hydroxylase NDUFAF5 could open doors to potential therapeutic strategies for these conditions.