Cryo-electron microscopy has reached resolution on par with X-ray crystallography

Compared to the more established X-ray crystallography, cryo-electron microscopy images were of lower resolution until a recent breakthrough that brought forth a “resolution revolution”. Specifically, advances in instrument setup, optics, and reconstruction software helped ushered in a new era in cryo-electron microscopy where resolution of images could reach 1.25 Angstrom. This is similar to that … More Cryo-electron microscopy has reached resolution on par with X-ray crystallography

Cryo-electron microscopy is still unable to capture the full motion of an enzyme undergoing catalysis

A holy grail in structural biology has been the capturing of movies that depict an enzyme undergoing catalysis, i.e., preferably with the enzyme in motion that captures a substrate, coverts it into a product, and releasing the product. To do so would require a method that could accurately image a protein with high resolution while … More Cryo-electron microscopy is still unable to capture the full motion of an enzyme undergoing catalysis

Experimental structural biology is still needed to verify predictions from computational structural biology

Understanding protein structure is fundamental to elucidating its function. But, difficulty in obtaining crystal structure and the sheer number of proteins available in nature meant that there remains a paucity of experimental structures of proteins available in public databases such as the Protein Data Bank. This then drove the development of computational structural biology tools … More Experimental structural biology is still needed to verify predictions from computational structural biology

Cryo-electron microscopy provides critical access to structures of membrane proteins compared to X-ray crystallography

Structures of membrane proteins are hard to determine by traditional approaches such as X-ray crystallography. This comes about due to the inherent flexibility of the transmembrane part of the membrane proteins that insert in between the hydrophobic tails of the phospholipid bilayer. While approaches such as stapling the hydrophobic parts of membrane proteins provide a … More Cryo-electron microscopy provides critical access to structures of membrane proteins compared to X-ray crystallography

Quality of homology structural model differs but quality of model is better for proteins with many solved experimental structures

Experimental structural biology techniques such as X-ray crystallography and cryo-electron microscopy have been the mainstay approaches for providing a view of the structures of many classes and types of protein. With improving instrumentation and enhanced speed for solving protein structures, there is a gradual but steady expansion of the collection of protein structures available in … More Quality of homology structural model differs but quality of model is better for proteins with many solved experimental structures

Sample preparation is key to successful cryo-electron microscopy imaging

Cryo-electron microscopy is often touted to be a more facile and accessible technique compared to X-ray crystallography given that it does not need the protein to be crystallised. However, the technique has its own set of challenges that significantly impact on the success rate of the method. One such challenge is sample preparation. In cryo-electron … More Sample preparation is key to successful cryo-electron microscopy imaging

Structural biology tools provide a snapshot of proteins frozen in time

Structural biology is one of the pillars of contemporary biology research given that it provides us with a view of the spatial arrangement of proteins and enzymes that help elude its physical function. Typically, X-ray crystallography and cryo-electron microscopy are used in elucidating the structure of proteins under defined conditions. But, it must be remembered … More Structural biology tools provide a snapshot of proteins frozen in time

Difficult to solve protein structures may require theoretical and experimental insights for solution

Cryo-electron microscopy has emerged as the go-to tool for solving structures of proteins that have previously defy crystallisation attempts. This comes about due to the facile nature in which cryo-electron microscopy could interrogate structures of proteins that have been snap frozen. However, not all protein structures can be determined via cryo-electron microscopy or the more … More Difficult to solve protein structures may require theoretical and experimental insights for solution

X-ray crystallography remains relevant as a structural biology technique

In contemporary structural biology, there is definitely a movement towards the deployment of cryo-electron microscopy for elucidating the structure of proteins. In particular, there are predictions that the number of structures solved by cryo-electron microscopy would exceed that of X-ray crystallography within the next decade. But, would X-ray crystallography be supplanted by cryo-electron microscopy and … More X-ray crystallography remains relevant as a structural biology technique

Citizen science mini-project: Understanding the structural basis of protein function

Objects around us each perform their unique functions. Not commonly known is that shape of objects plays an important role in enabling different objects to perform different functions. The same is true for proteins. Different proteins perform different functions, and each structured differently. Indeed, shape defines function, in proteins, and in objects around us. This … More Citizen science mini-project: Understanding the structural basis of protein function