Automatic analysis tool for ligand screening NMR data

Screen 2.0 introduces a redesigned interface that enhances user experience and simplifies result analysis. It also features the new Screen DB, a structured database for saving and organizing results, creating a valuable knowledge resource. Users can now easily compare current results with past screening experiments, review their experimental history, and streamline future workflows for increased efficiency.

To streamline the screening workflow, we have introduced Mix Design, an auxiliary feature of the Screen plugin, used to design mixtures of compounds with minimal overlap in their NMR signals. It is a common practice to pool 6-10 compounds together for ¹H experiments, or 20-40 compounds for ¹⁹F experiments, to reduce both the measurement time and the amount of target protein required (and hence the cost). However, when analyzing such data, minimal peak overlap is critical for deconvoluting the mixture and identifying the hits reliably. ​

Mnova Screen can handle all data from the following screening experiments:

• ¹H or ¹⁹F
•  Single compounds or mixtures
•  With or without reference spectra
•  Single or multiple types of spectra (STD, T1ρ, wLOGSY, CPMG)
•  Use of Blank, w/ Protein, & w/ Protein+ Inhibitors
•  Automatic hit specificity detection based on results of Protein + Inhibitor experiments

The spectral data can be raw or processed data from various vendors (Bruker, Varian/Agilent, JEOL, JCAMP etc.)

Data organization is crucial for batch processing. Mnova Screen must::
— Identify the mixture/screen data for each sample and recognize their type.
— Find and associate reference spectra with the mixture data.

Screen uses a Master Data File to organize everything in the correct format. Mestrelab can assist with custom scripts to reorganize your data. If using FBS, a Master Data File (JSON) can be generated automatically, streamlining raw data import.

Example of hit detection in a ¹⁹F Screen using CPMG experiments: ligands blank (1), ligands with protein (2), and ligands with protein and inhibitor (3).

• Blue: Specific hits—CPMG intensity decreases from (1) to (2), with recovery from (2) to (3).
• Green: Non-specific hits—CPMG intensity decreases from (1) to (2), with no significant recovery from (2) to (3).
• Yellow: Present—no significant intensity decrease from (1) to (2).
• Red: Missing—peaks not matched in (1).