The Diamond Light Source and the challenges ahead for structural biology: some informal remarks

Abstract

The remarkable advances in structural biology in the past three decades have led to the determination of increasingly complex structures that lie at the heart of many important biological processes. Many of these advances have been made possible by the use of X-ray crystallography using synchrotron radiation. In this short article, some of the challenges and prospects that lie ahead will be summarized.

Extension of the transferable aspherical pseudoatom data bank for the comparison of molecular electrostatic potentials in structure–activity studies

“…Studies of molecular and crystal electrostatic potential are currently gaining more and more attention due to the technological and methodological revolution in the field of electron microcopy (Henderson, 1995;Ramakrishnan, 2015;Brown et al, 2014;Thomas et al, 2001;Midgley & Thomas, 2014) Nowadays, it is possible to obtain a crystal or singlemacromolecule 3D structure with atomic or near-atomic resolution (Tan et al, 2018;Bartesaghi et al, 2018;Jones et al, 2018). It is the electrostatic potential which scatters the electron beam.…”

Developments in Structural Chemistry from the Viewpoint of a Solid‐state Chemist: A Review Prompted by the Sixtieth Anniversary of Professor Jack Dunitz's Research Group in the ETH, Zurich

“…This is the essence of cryo‐electron microscopy (cryo‐EM), and this technique has, as explained by Henderson,, experienced a quantum leap in its capability in recent years, owing to improved microscopes, better detectors and superior software. It is now possible to obtain near‐atomic resolution 3D density maps of macromolecular assemblies using single‐particle cryo‐EM without the need of crystals ,. Figure illustrates the power of this cryo‐EM technique.…”

“…As a solid‐state chemist who has for almost my entire scientific career utilized electron microscopy as a chemical technique, it pleases me to note the profound impact that present‐day developments in EM is having both in the biological and physical aspects of structural chemistry. Even structures of extreme complexity, such as large ribosomal subunits from human mitochondria (revealing 48 proteins) have been elucidated at 3.4 Å resolution using single‐particle cryogenic EM ,. And the femtosecond scale, dynamic electron microscopy introduced by Zewail et al ., is currently revolutionizing the whole corpus of structural physical science.…”