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Updated: Jan 22, 2026
14:44
Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
Published on: December 16, 2013
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Modeling pH-Dependent NMR Chemical Shift Perturbations in Peptides
Efrosini Artikis1, Charles L Brooks2
1Biophysics Program, University of Michigan, Ann Arbor, Michigan.
Biophysical Journal
|July 1, 2019
Summary
This study models pH effects on protein and peptide chemical shifts, crucial for understanding structure-function. The new method accurately predicts pH-dependent chemical shift perturbations (CSPs) using molecular dynamics and quantum mechanics.
Area of Science:
- Biophysical Chemistry
- Computational Chemistry
- Structural Biology
Background:
- Accurate modeling of protein and peptide chemical shifts is vital for understanding structure-function relationships.
- Current chemical shift prediction software often lacks capabilities for pH dependence outside physiological ranges.
- Protonation state changes significantly impact molecular conformation and properties.
Purpose of the Study:
- To develop and validate a computational method for predicting pH-dependent chemical shift perturbations (CSPs) in peptides.
- To investigate the contributions of through-space and through-bond interactions to CSPs.
- To provide a foundation for improving empirical and semiempirical chemical shift prediction tools.
Main Methods:
- Combined molecular dynamics (MD) and quantum mechanics (QM) simulations.
- Altered protonation states of titratable groups in model tripeptides.
- Computed chemical shifts and conformational ensembles.
Main Results:
- Significant CSPs were observed for nuclei near protonation sites.
- The method accurately recapitulated experimental pH-dependent CSPs (R = 0.85 for 13C, 0.99 for 15N, 0.98 for 1H).
- Protonation state changes induced notable differences in conformational ensembles.
Conclusions:
- The study successfully demonstrates a method to model pH-dependent chemical shifts in peptides.
- This work lays the groundwork for incorporating pH effects into chemical shift prediction software.
- The findings enhance the understanding of how protonation influences peptide structure and dynamics.
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