Simulation of oriented NMR spectra: Combining molecular dynamics and chemical shift tensor calculations

Area of Science:

• Biophysics
• Structural Biology
• Nuclear Magnetic Resonance (NMR) Spectroscopy

Background:

• Solid-state NMR, specifically PISEMA experiments, is crucial for determining protein and peptide orientation in lipid bilayers.
• Interpreting PISEMA spectra can be challenging for systems lacking perfect α-helical structures or exhibiting molecular motion.

Purpose of the Study:

• To develop and validate a novel computational method for simulating and interpreting PISEMA-like NMR spectra.
• To accurately model spectra from molecules with non-ideal secondary structures and heterogeneous dynamics.

Main Methods:

• A new method combining molecular dynamics simulation with tensorial orientational constraints (MDOC) and chemical shift tensor calculations was developed.
• The approach involves simulating molecular reorientations and optimizing structures using Bond Polarization Theory (BPT) for ¹⁵N chemical shift tensor data.
• Averaged dipolar couplings and δ_zz tensor components were used to simulate PISEMA patterns.

Main Results:

• The developed method successfully simulates PISEMA spectra for non-α-helical molecules and those with mobility variations.
• Application to gramicidin A (gA) enabled assignment of most PISEMA resonances.
• MDOC simulations provided local order parameters, highlighting significant backbone mobility differences between L- and D-amino acids in gA.

Conclusions:

• The MDOC method offers a powerful tool for analyzing complex solid-state NMR spectra where traditional methods fall short.
• This approach enhances the interpretation of PISEMA data for peptides and proteins with diverse structural and dynamic properties.
• The findings provide insights into the local dynamics of gramicidin A, differentiating between L- and D-amino acid contributions.