Hydrogen density mapping in biomolecular crystals through dynamic nuclear polarization

Area of Science:

• Structural Biology
• Biophysics
• Crystallography

Background:

• Fundamental biological processes rely on hydrogen atoms, but conventional X-ray crystallography poorly resolves them.
• Neutron macromolecular crystallography (NMC) offers superior sensitivity to hydrogen and deuterium for atomic resolution.
• Accurate hydrogen atom positioning is critical for understanding biological reaction mechanisms.

Purpose of the Study:

• To present a theoretical framework for dynamic nuclear polarization NMC (DNP-NMC) techniques.
• To enhance the resolution and signal contribution of hydrogen atoms in biomolecular crystals.
• To improve the accuracy of neutron structure determination.

Main Methods:

• Developing DNP-NMC by aligning neutron and proton nuclear spins.
• Establishing key relationships for the coherent structure factor of polarized neutron scattering.
• Utilizing a hybrid input/output phase-retrieval algorithm for hydrogen density recovery.

Main Results:

• The DNP-NMC approach advances H atom resolution in protein residues and solvent.
• Theoretical phase reconstruction accuracy is achieved, improving neutron structure determination.
• Hydrogen density recovery with >90% phase accuracy is demonstrated.

Conclusions:

• DNP-NMC offers a significant advancement for resolving hydrogen atoms in biomolecular structures.
• The method provides a path to achieve >80% accuracy in neutron structure determination.
• Experimental considerations for upcoming DNP-NMC experiments are discussed.