Biomolecular imaging and electronic damage using X-ray free-electron lasers

Abstract

The challenges involved in determining the structures of molecules to atomic resolution in non-crystalline samples using X-ray free-electron laser pulses are formidable 1 . Proposals to determine biomolecular structures from diffraction experiments using femtosecond X-ray free-electron laser pulses involve a conflict between the incident brightness required to achieve diffraction-limited atomic resolution and the electronic and structural damage induced by the illumination. Significant advances have already been made, however, in the design and preparation of experiments using fourth-generation sources 2 and the corresponding structural analysis of diffraction data. Here we show that previous estimates of the conditions under which biomolecular structures may be obtained in this manner are unduly restrictive, because they are based on a coherent diffraction model that is not appropriate to the proposed interaction conditions. A more detailed imaging model derived from optical coherence theory and quantum electrodynamics is shown to be far more tolerant of electronic damage. The nuclear density is employed as the principal descriptor of molecular structure. The foundations of the approach may also be used to characterize electrodynamical processes by carrying out scattering experiments on complex molecules of known structure. © 2011 Macmillan Publishers Limited. All rights reserved.