X-ray photon correlation spectroscopy of protein dynamics at nearly diffraction-limited storage rings

Abstract

This study explores the possibility of measuring the dynamics of proteins in solution using X-ray photon correlation spectroscopy (XPCS) at nearly diffraction-limited storage rings (DLSRs). We calculate the signal-to-noise ratio (SNR) of XPCS experiments from a concentrated lysozyme solution at the length scale of the hydrodynamic radius of the protein molecule. We take into account limitations given by the critical X-ray dose and find expressions for the SNR as a function of beam size, sample-to-detector distance and photon energy. Specifically, we show that the combined increase in coherent flux and coherence lengths at the DLSR PETRA IV yields an increase in SNR of more than one order of magnitude. The resulting SNR values indicate that XPCS experiments of biological macromolecules on nanometre length scales will become feasible with the advent of a new generation of synchrotron sources. Our findings provide valuable input for the design and construction of future XPCS beamlines at DLSRs.

Towards molecular movies with X-ray photon correlation spectroscopy

“…MBA based storage rings also provide smaller source sizes, which allow to use large and coherent beams important for reducing photon density and mitigating beam damage. 22 XPCS experiments can also be performed at superconducting XFELs such as the LCLS-II or the European XFEL taking advantage of the MHz repetition rate and the high-pulse brilliance of these sources. By using the split-and-delay technique 10,70,81,82 time scales on the order of the pulse duration on the 100 fs scale and below are accessible.…”

“…Here, we give a perspective on future exciting science questions in connection to biological aqueous solutions that can be addressed with XPCS at the new X-ray sources. [21][22][23] Specifically, we discuss the importance of understanding biomolecular condensates on the nanoscale and the role of the heterogeneities of liquid and supercooled water in biological activity. Furthermore, we highlight the state of the art XPCS capabilities and provide practical considerations for designing XPCS experiments.…”

Potential and limits of a colloid approach to protein solutions

“…We need significant methodological development, including developing both advanced coarse-graining approaches in simulation and a combination of several experimental methods such as NSE and X-ray photon correlation spectroscopy (XPCS). 177 This needs to go hand in hand with the development of new sample environments to account for the very limited quantities of proteins typically available for such investigations, and the design of new measurement and data analysis procedures to overcome the notorious beam damage problem when working with intense synchrotron radiation.…”

Diffusive dynamics of Aspartateα-decarboxylase (ADC) liganded with D-serine in aqueous solution

“…There are multiple ways to probe these dynamics, including experiments that examine the macromolecule as it proceeds through its reaction cycle [6,7], as well as methods that probe the equilibrium or nondriven dynamics [8]. However, many of the experimental tools to probe equilibrium dynamics require incorporation of labels, can access only dilute macromolecular suspensions, or cause radiation damage [9,10]. Quasi-elastic neutron scattering (QENS) has been shown to be sensitive to the functionally relevant intra-and intermolecular dynamics of proteins [11,12,13], and how these dynamics change in response to ligand binding [14] or covalent modification [15].…”