Molecular structure refinement based on residual dipolar couplings using magnetic-field rotational sampling

Area of Science:

• * Biophysical Chemistry
• * Structural Biology
• * Computational Chemistry

Background:

• * Residual dipolar couplings (RDCs) are valuable for molecular structure determination.
• * Traditional methods often rely on alignment tensors, assuming molecular rigidity and decoupled motion.
• * These assumptions can limit the accuracy of structure refinement, especially for flexible molecules.

Purpose of the Study:

• * To develop a novel method for molecular structure refinement using RDC data.
• * To avoid the limitations of alignment tensors by incorporating experimental conditions.
• * To investigate the impact of molecular flexibility and RDC data quality on structure refinement.

Main Methods:

• * Calculation of RDC values via magnetic-field rotational sampling and internal configurational sampling.
• * Application of rotational sampling mirroring experimental conditions.
• * Testing the method on rigid and flexible cyclo-octane molecules as toy models.

Main Results:

• * The method accurately reflects molecular flexibility and reduces reliance on the alignment tensor.
• * Molecular flexibility, force-field choice, and RDC data quantity influence refinement outcomes.
• * Magnetic-field rotational sampling proves efficient and less dependent on the number of RDC restraints.

Conclusions:

• * The proposed method offers a more experimentally relevant approach to RDC-based structure refinement.
• * Molecular flexibility significantly impacts the reliability of RDC-derived structures.
• * The study highlights inherent limitations in the information content of RDCs for precise molecular structure determination.