KENBIKYO Vol.53▶No.1 2018
■Feature Articles: A New Era of Electron Cryo-Microscopy for Life Science

Cryo-EM System for Supporting Drug Discovery and Life Sciences

Naoyuki Miyazaki, Mika Hirose, Kiyo Tsunezumi, Akifumi Higashiura, Atsushi Nakagawa and Kenji Iwasaki

Abstract: Recently, electron cryo-microscopy single particle analysis (cryo-EM SPA) has been developed dramatically and can be used for drug design because of the greatly improved resolution to near-atomic level. Nowadays, based on the atomic structures of drugs within the target protein molecules, the drugs can be designed or modified more efficiently, which is called as structure-based drug design (SBDD). We have constructed a cryo-EM system for supporting collaborations for drug discovery and life sciences, mainly supported by and used for national platform projects of BINDS and PDIS, AMED. For example, structures of a virus-like particle of PfV (Pyrococcus furiosus virus-like particle) of 30 nm in diameter have been determined at near-atomic resolutions (3.3 Å) by both conventional cryo-EM (CTEM) and Volta phase contrast cryo-EM (VPC-TEM) SPA methods within a week. In addition to the high-throughput structure analysis, we succeeded high-resolution cryo-EM SPA at 2.3 Å resolution with an advanced direct electron detecting camera, Falcon 3EC in an electron counting mode. Here, we introduce our cryo-EM system for the high-throughput and high-resolution single particle analyses.

Key words: electron cryo-microscopy, single particle analysis, near-atomic resolution, high throughput structure analysis