NMR Spectral Similarity Map for Structural Change Detection
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Solution Overview
Problem
Current methods for detecting structural changes in molecules using NMR spectroscopy are inadequate for reliably distinguishing between changes in the molecule itself and its environment, particularly in biopharmaceuticals like proteins, where shifts and broadenings of peaks can indicate quality deviations due to handling or storage issues.
Innovation Solution
A computer-implemented method that processes n-dimensional NMR spectra by selecting similarity regions around spectrum points, computing local similarity values using functions like Pearson correlation or cosine similarity, and generating similarity maps to differentiate between structural changes in the molecule and its environment, allowing for visualization and filtering of indicators for peak shifts and broadenings.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional NMR spectroscopy methods are used to detect structural changes in molecules, then information about molecular structure and environment is obtained, but the ability to reliably distinguish between molecular changes and environmental changes is insufficient
Solution Approach 1:
The patent segments the NMR spectrum into multiple local regions around selected spectrum points. For each region, it computes local similarity values between reference and test spectra, then generates a similarity map that segments the overall detection task into localized comparisons. This segmentation enables precise identification of whether changes occur in molecular peaks or environmental background, resolving the contradiction between detection precision and information loss.
2Loss of information
If multidimensional NMR spectra are analyzed to obtain detailed molecular information, then structural details are improved, but the complexity of distinguishing molecular changes from environmental changes increases
Solution Approach 1:
The patent introduces a similarity map as an intermediary between the raw multidimensional NMR spectra and the final structural change detection. This similarity map computationally processes the complex spectral data, highlighting only the relevant differences between reference and test spectra while filtering out environmental noise. The intermediary transforms complex spectral analysis into a more manageable form, maintaining information retention while reducing analytical complexity.
3Difficulty of detecting and measuring
If peak shifts and broadenings are monitored to detect structural changes, then detection capability is improved, but reliability in distinguishing molecular changes from environmental effects deteriorates
Solution Approach 1:
The patent applies local quality by computing similarity values specifically around selected spectrum points rather than analyzing the entire spectrum uniformly. Each local region is evaluated independently, allowing the system to focus on specific peaks of interest while ignoring irrelevant environmental variations. This localized approach improves both the ease of detection and the reliability by concentrating analytical resources on molecularly significant regions.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables reliable and efficient identification of structural changes in test molecules compared to reference molecules, reducing errors by clearly distinguishing between molecular and environmental changes, thus ensuring the quality of biopharmaceuticals.
Implementation Method 1
Nuclear magnetic resonance (NMR) spectroscopy is a spectroscopic technique to observe local magnetic fields around atomic nuclei. A sample is placed in a magnetic field and the NMR signal is produced by excitation of the nuclei sample with radio frequency (RF) pulses into nuclear magnetic resonance
Implementation Method 2
the NMR signal is produced by excitation of the nuclei sample with radio frequency (RF) pulses into nuclear magnetic resonance, which is detected with sensitive RF receivers
Data Source
AI summary
A system, method and computer program product for detecting indicators for structural changes of NMR active test molecules in a test sample, or indicators for structural changes of the environment of said test molecules in relation to a reference molecule. Initial local similarity values are obtained, using a similarity function and representing a local similarity between a reference spectrum and a test spectrum within corresponding similarity regions (SRR, SRT). The initial local similarity values represent a similarity map (SM1) in which contours of a first shape type are indicators (I1) for structural changes of the test molecule, and in which contours of a second shape type are indicators (I2) for structural changes of the environment of said test molecule in relation to the reference molecule.