Neutron diffraction experiments on aqueous solutions of molecular species, such as sugars and amino acids, are notoriously difficult to interpret due to the complexity of the data obtained. A new approach, combining neutron diffraction with isotopic substitution experiments on specifically-labelled samples with molecular dynamics simulations, makes it possible to fully understand the structure of these biomolecules in the water environment.

The technique of neutron scattering with isotopic substitution (NDIS) can be used to reduce the data into the structural correlations between one atom type and all other atom types in the system. Unfortunately, in a large chiral molecule like glucose, replacement of the non-exchangeable hydrogen atoms with deuterium still leaves a complicated average structure factor since each of these atoms is in a different structural environment. However, exploiting the beam intensity and instrument stability available at ILL, it is possible to design an NDIS experiment that overcomes these difficulties. By synthesizing a glucose sample with deuterium substituted at only one non-exchangeable position, it is possible to obtain diffraction data for the environment around that specific site with acceptable counting statistics. Even these highly specific structural data cannot be interpreted without further information.

With the help of parallel molecular dynamics simulations on an identical system, however, the different peaks in the experimental radial correlation function can be assigned, making it possible to interpret the diffraction data in terms of specific correlations between pairs of individual atoms.

P.E. Mason et al, ILL Annual Report 2006, p.48-49