Application of maximum entropy method to neutron protein crystallography

Hydrogen atoms or hydrogen bonds play important roles in protein functions. Neutron diffraction is very powerful tool to detect hydrogen atoms. However it is often obtained rather poor resolution data compared with X-ray data due to weak neutron source intensity and large incoherent scattering from hydrogen atoms. The maximum entropy method (MEM) is noble method to obtain high resolution electron or nuclear density distribution from even limited number of diffraction data. The MEM has been applied to not only X-ray data of small molecules but also those of proteins. For the application to neutron data, so far, only small molecules are reported. When preliminary application of the MEM to 1.1 Å resolution partially deuterated neutron protein data (Protein Data Bank ID : 4fc1) is carried out, most of hydrogen and deuterium atoms are observed (Fig. 1). Since this resolution is unusually high, it is of interest that ability of the MEM for usual or low resolution data. In this paper, effects of resolution and data quality for the MEM are examined. Large deuterated crystals are necessary for neutron experiment to reduce incoherent scattering from hydrogen atoms and to improve data resolution. However deuterated condition is not usual for biomolecules. If no deuteration is need for low resolution data by using the MEM, it would be able to observe biomolecules as they are.

The 100 Years History of Crystallography in Japan

A century ago, crystallogtaphy ushered in the era of modern science & technology in Japan. The beginning of modern crystallography in Japan dates back to 1913. Torahiko Terada (Tokyo Imperial University) demonstrated X-ray diffraction[1] and Shoji Nishikawa (Tokyo Imperial University) reported on X-ray patterns of fibrous, lamellar and granular substances[2]. In 1936, Ukichiro Nakaya (Hokkaido University) successfully classified natural snow crystals and made the first artificial snow crystals. In the last half-century, developments in crystallography helped form thriving manufacturing sectors such as the semiconductor industry, the iron and steel industries, the pharmaceutical industry, the electronics industry, the textile industry, and the polymer industry, as well as a wide array of academic research.

Japanese Crystallography in Culture and Art

"We can find many seeds of crystallography in Japanese culture. Most of the family crests have symmetry elements such as rotation axes and mirror symmetry elements. Sekka-zue, a picture book of 86 kinds of crystals of snow, was made by Toshitura Doi, who is a feudal lord in Edo-period and he observed snow using a microscope in nineteenth century. In recent years, people enjoy to make crystal structures, polyhedrons, carbon nanotube, quasicrystal etc. by origami, the art of folding paper [1]. In the field of science, the Japanese crystallography has contributed to explore culture and art. An excellent example is unveiling the original color of Japanese painting "Red and White Plum Blossoms" by Korin Ogata [2]. Prof. Izumi Nakai (Tokyo University of Science) developed an X-ray fluorescence analyzer and an X-ray powder diffractometer designated to the investigation of cultural and art works and had succeeded in reproducing the silver-colored waves through computer graphics after X-ray analyses of crystals on the painting. The scientific approach by Prof. Nakai et al. unveiled the mystery of cultural heritage of ancient near east, ancient Egypt etc. and is being to contribute to insight into the history of human culture. [1] An event to enjoy making crystals by origami is under contemplation. [2] The symposium ""Crystallography which revives heritages"" was held on February 16, 2014 at Atami in Japan."

Japanese Science & Technology with Crystallography

Divers Japanese Science and Technology has advanced together with the progress of crystallography in biology, chemistry, physics, materials science, metallurgy, electronics, engineering, geoscience, etc. Based on the highly scientific and crystallographic technology, Japan has been a great contributor in developing of high-end X-ray generator, electron microscope as well as large scale Photon Science facilities, such as Photon Factory (SR), SPring-8 (SR), J-PARC (Neutron) and SACLA (XFEL). Under such background, we promote IYCr2014 with the partnership of 36 academic societies in the field of pure and applied sciences. In the last half-century, developments in crystallography have also helped thriving manufacturing sectors such as the semiconductor, the iron and steel, the pharmaceuticals, the electronics, the textile, and the chemical industries. Some of the recent impressive outcomes in Japan are fundamental findings of photosynthesis [1] and pristine asteroid [2]. Crystallography in Japan keeps promoting our nationwide projects grappling with global problems such as environment and food, and will contribute to realize a sustainable society.

Neutron powder diffraction analysis of guanosine dihydrate using MEM

In majority of the crystals of pharmaceutical compounds, hydrogen bonds play a crucial role. Determination of a hydrogen position is highly important, in order to investigate hydrogen bonds especially in the case of hydrates. We have been investigating humidity-induced phase transitions of hydrates systematically [1,2]. Unique characteristics of hydration water molecules have prompted us to explore the phenomena more precisely. Neutron diffraction analysis is a powerful tool to determine hydrogen positions. However, large single crystals are required because of weak neutron diffraction intensities. Under such background, we carried out neutron powder diffraction analysis of guanosine dihydrate using the Maximum Entropy Method (MEM). Neutron powder diffraction data of guanosine dihydrate (C10H13N5O5.2H2O; crystal data: monoclinic, space group P21, a = 17.518, b = 11.278, c = 6.658 Å, β= 98.17⁰, Z = 4) were measured by iMATERIA at MLF in J-PARC (Figure 1(a)). Rietveld analysis was carried out using atomic coordinates of non-hydrogen atoms determined by X-ray analysis and those of hydrogen atoms which were placed on the geometrically calculated positions using the averaged X-H bond lengths determined by neutron analysis referencing the hydrogen positions estimated by X-ray analysis. Using Fo and σ by Rietveld analysis, the nuclear density distribution was calculated by MEM (Figure 1(b)). Nuclear densities of the hydrogen atoms of one water molecule (W1 in Figure 1) were elongated, which is consistent with the results of molecular dynamic simulation [2]. The effective usage of MEM to elucidate hydrogen atom positions from neutron powder diffraction data will be discussed together with that of difference Fourier calculations.