Advances and opportunities in ultrafast X-ray crystallography and ultrafast structural optical crystallography of nuclear and electronic protein dynamics.

Jasper J. van Thor

doi:10.1063/1.5110685

Abstract

Both nuclear and electronic dynamics contribute to protein function and need multiple and complementary techniques to reveal their ultrafast structural dynamics response. Real-space information obtained from the measurement of electron density dynamics by X-ray crystallography provides aspects of both, while the molecular physics of coherence parameters and frequency-frequency correlation needs spectroscopy methods. Ultrafast pump-probe applications of protein dynamics in crystals provide real-space information through direct X-ray crystallographic structure analysis or through structural optical crystallographic analysis. A discussion of methods of analysis using ultrafast macromolecular X-ray crystallography and ultrafast nonlinear structural optical crystallography is presented. The current and future high repetition rate capabilities provided by X-ray free electron lasers for ultrafast diffraction studies provide opportunities for optical control and optical selection of nuclear coherence which may develop to access higher frequency dynamics through improvements of sensitivity and time resolution to reveal coherence directly. Specific selection of electronic coherence requires optical probes, which can provide real-space structural information through photoselection of oriented samples and specifically in birefringent crystals. Ultrafast structural optical crystallography of photosynthetic energy transfer has been demonstrated, and the theory of two-dimensional structural optical crystallography has shown a method for accessing the structural selection of electronic coherence.

Highlights

The desire to create “molecular movies” of protein function has driven rapid technological advances in the area of ultrafast crystallography
This perspective aims to discuss together the different structural aspects of molecular processes that are detected in X-ray crystallographic and ultrafast and nonlinear structural optical crystallography
A snapshot of developments in the different related areas of ultrafast structural dynamics is given with an emphasis on protein dynamics and single crystal applications

Summary

Introduction

The desire to create “molecular movies” of protein function has driven rapid technological advances in the area of ultrafast crystallography. Ultrafast X-ray crystallography and ultrafast structural optical crystallography provide access to molecular transformations on the coherent time scale and are both highly selective in their observations. This is the key point and focus of this contribution, to discuss their complementary nature and identify opportunities for future developments. Enabled by the advent of X-ray Free Electron laser (XFEL) sources operating at Angstrom wavelengths and beamline technology, it has become possible to perform femtosecond time resolved pump-probe experiments revealing ultrafast structural dynamics.[1,2,3] that time resolved X-ray crystallography is possible in the coherent time domain, fundamental questions regarding the control, assignment, and analysis of ultrafast motion have arisen. Ultrafast pump-induced differences are generally isomorphous in the case of protein crystals, which allows the generation of Fourier-difference analysis of electron density changes.[1,2,3] The ultrafast time scale is not always a requirement for the observation of isomorphous differences following illumination, with many examples from the synchrotron-based and XFEL-based time resolved crystallography with longer pump-probe delays as well.[4,5,6,7,8,9,10,11,12,13,14]

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Conclusion