NMX

Macromolecular Diffractometer

The NMX macromolecular diffractometer will open new avenues for structural biology with neutrons. Determining hydrogen atom positions faster than before from smaller crystals and larger unit cells than before will allow studies of more challenging systems such as transmembrane proton pumps. This will yield an improved understanding of not only fundamental biological processes such as energy production in cells, but also the way in which pharmaceuticals bind their target proteins.

Instrument Class

Diffraction

Beam Port Allocation

W1

Lead Scientist

Esko Oksanen

Lead Engineer

Giuseppe Aprigliano

The NMX Macromolecular Diffractometer is a time-of-flight (TOF) quasi-Laue diffractometer optimised for small samples and large unit cells dedicated to the structure determination of biological macromolecules by crystallography. The main scientific driver is to locate the hydrogen atoms relevant for the function of the macromolecule.

Figure 2. Neutron crystallography allows unambiguous determination of hydrogen positions, including the ordered water hydrogens. This example shows a hydrogen bonding network from the enzyme urate oxidase.

Oksanen et al. 2014

The ESS long pulse source is well suited for a quasi-Laue macromolecular diffractometer that can spread the background in the TOF dimension, while the Bragg peaks are observed at a defined TOF. Therefore a macromolecular diffractometer at the ESS could be used either to study systems with smaller crystals or larger unit cell volumes. Growing well-ordered protein crystals of cubic millimeter volume is extremely difficult, so the instrument is optimised for submillimeter crystal sizes.

One of the limiting factors with current instruments is that the fixed detector geometry only allows a maximal unit cell edge of ~150 Å to be resolved without a compromise in the diffraction resolution (dmin). The NMX instrument allows larger unit cells to be resolved by increasing the crystal-to-detector distance. This incurs an increase in the data collection time, but reflections to the same dmin can still be observed by swinging the detector in scattering angle 2q. Many of the scientifically most interesting systems, such as proton pumping membrane proteins, crystallise in large unit cells, so simply being able to resolve a large unit cell edge is a unique advantage. The combination of a neutron flux comparable to leading high flux reactor instruments, such as LADI-III, together with time-of-flight expansion, the ability to resolve large unit cells and the ability to separate signal from background leads to world-leading performance particularly with the experimentally most challenging systems. The ESS NMX instrument will transform neutron macromolecular crystallography into a technique that answers a significantly larger number of hydrogen-related questions in biomolecular science than before.

The NMX Macromolecular Diffractometer is a single crystal diffractometer using the quasi-Laue time-of-flight (TOF) technique.

Figure 1. The layout of the NMX instrument showing the neighbouring instrument BEER and the main technical components inside the experimental cave

The main parts of the instrument are:

  • the beam transport and conditioning system (BTS) that delivers the neutron beam to the sample position in the experimental cave
  • the sample exposure system (SES) that positions the sample crystal in the neutron beam
  • the scattering characterisation system (SCS) that detects the diffracted neutrons

The BTS consists of a neutron guide system where a curved part (Figure 1) loses the line-of-sight to the neutron moderator inside a common shielding bunker and a straight part delivers the beam to the experimental cave. A chopper system selects the desired neutron wavelengths. Inside the experimental cave a collimation system tailors the divergence and size of the neutron beam to match the sample properties—the beam size can be selected with a pinhole exchanger (Figure 1). The sample is positioned and rotated with a robotic sample positioner (Figure 1) and the three 50 x 50 cm detector panels are also mounted on six-axis robots. The experiment will be controlled and samples prepared in an adjacent control hutch.

We expect that at 2 MW ESS accelerator power it will be possible to collect a diffraction data set to ca. 2 Å resolution and >90% completeness in a day from a crystal of < 0.1 mm3 volume (ca. 0.5 mm linear dimension) and unit cell dimensions < 150 Å. We expect that data collection should be possible from significantly smaller crystals or larger unit cells in several days.

Data collection will be possible at ambient as well as cryogenic temperatures and a humidity control device is foreseen.

The NMX team at IKON13 in Lund, September 2017

ESS

ESS

Esko Oksanen

Inst. Sci. - Macromol Crystallography

ESS

Giuseppe Aprigliano

Mechanical Engineer

ESS

Dorothea Pfeiffer

Physicist Engineer

ESS

Valentina Santoro

Neutron Beam and Shielding Scientist

ESS

Markus Olsson

Mechanical Engineer

ESS

Partners

  • Márton Markó
    Scientist
    Wigner Research Center for Physics of the Hungarian Academy of Sciences
  • Endre Kosa
    Engineer
    Wigner Research Center for Physics of the Hungarian Academy of Sciences
  • Szabina Török
    Senior Scientist
    Energy Research Centre of the Hungarian Academy of Sciences
  • Peter Zagyvai
    Senior Scientist
    Energy Research Centre of the Hungarian Academy of Sciences
  • Gábor Nafradi
    Scientist
    Energy Research Centre of the Hungarian Academy of Sciences
  • Jean-Luc Ferrer
    Senior Scientist
    Institut de Biologie Structurale, Commissariat à l’énergie atomique et aux énergies alternatives (CEA)
  • Petri Kursula
    Senior Scientist
    University of Bergen