Algorithmic framework for X-ray nanocrystallographic reconstruction in the presence of the indexing ambiguity

Abstract

X-ray nanocrystallography allows the structure of a macromolecule to be determined from a large ensemble of nanocrystals. However, several parameters, including crystal sizes, orientations, and incident photon flux densities, are initially unknown and images are highly corrupted with noise. Autoindexing techniques, commonly used in conventional crystallography, can determine orientations using Bragg peak patterns, but only up to crystal lattice symmetry. This limitation results in an ambiguity in the orientations, known as the indexing ambiguity, when the diffraction pattern displays less symmetry than the lattice and leads to data that appear twinned if left unresolved. Furthermore, missing phase information must be recovered to determine the imaged object's structure. We present an algorithmic framework to determine crystal size, incident photon flux density, and orientation in the presence of the indexing ambiguity. We show that phase information can be computed from nanocrystallographic diffraction using an iterative phasing algorithm, without extra experimental requirements, atomicity assumptions, or knowledge of similar structures required by current phasing methods. The feasibility of this approach is tested on simulated data with parameters and noise levels common in current experiments.