Molecular structures from femtosecond x-ray pulses

Abstract

In this issue of PNAS Miao, Hodgson, and Sayre (1) validate a method of three-dimensional structure determination for individual biological macromolecules. Their proposal, based on suggestions by Hajdu and colleagues (2), is supported by careful computer simulation using plausible assumptions, and rests on recent advances in a number of related fields. In brief, they adopt the idea that femtosecond (fsec) x-ray pulses generated by free electron, laser-based x-ray sources will allow the two-dimensional (2D) diffraction patterns (DPs) of individual molecules to be recorded (2). Appropriate registration and averaging of these patterns will allow the full three-dimensional DP of the molecule to be assembled into an effectively continuous function. Previous work by Sayre and colleagues (3, 4) and others (5) has shown that, for objects that are everywhere positive and that are confined to an envelope of known size, the phases of the continuous diffraction pattern can be recovered. Thus, an image of the molecule can be formed by Fourier transformation of the phased diffraction pattern. The quality of the images produced in the simulation is quite high, and generated a burst of pleasure and optimism in this commentator.