Simulations of single-particle imaging of hydrated proteins with x-ray free-electron lasers

We employ start–to-end simulations to model coherent diffractive imaging of single biomolecules using x-ray free electron lasers. This technique is expected to yield new structural information about biologically relevant macromolecules thanks to the ability to study the isolated sample in its natural environment as opposed to crystallized or cryogenic samples. The effect of the solvent on the diffraction pattern and interpretability of the data is an open question. We present first results of calculations where the solvent is taken into account explicitly. They were performed with a molecular dynamics scheme for a sample consisting of a protein and a hydration layer of varying thickness. Through R–factor analysis of the simulated diffraction patterns from hydrated samples, we show that the scattering background from realistic hydration layers of up to 3 Å thickness presents no obstacle for the resolution of molecular structures at the sub–nm level.

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