Secondary Structure Elucidation via X-Ray Cross Correlation Analysis

Abstract

We aim to measure substantial structural information via X-ray scattering in the absence of an ordered system. Instead of a crystal, which consists of N particles at a single orientation relative to the X-ray beam, our samples consist of N randomly oriented identical particles. Assume, in a given exposure, two (or more) photons scatter from the same particle in a time interval much less than the rotational diffusion time, i.e. while the particle orientation is fixed. These two photons are correlated via the structure of the particle. By time averaging intensity correlations from such measurements, one can hope to recover structural information of the single scatterer relative to the background of N randomly oriented scatterers. One can demonstrate the high-dimensional data obtained from such a correlation experiment exceeds that measured in small and wide angle X-ray scattering measurements.We have performed measurements on gold nanoparticle solutions at the Linac Coherent Light Source (LCLS) and are using them to identify and overcome the challenges involved in CXS experiments. Imperfections in detector geometry and electronic response can contribute to false correlations in the data; we are developing ways of identifying and removing these artifacts. We are simultaneously gauging our ability to recover protein secondary structural information from such data. Nanoparticle scattering will serve as a benchmark for an upcoming experiment at the Spring-8 Angstrom Compact free electron laser (SACLA), where we will attempt to measure correlated scattering from F-actin. Thereafter we hope to refine current models of the F-actin polymer by fitting them against our high dimensional data.