Computational protein design provides insights that enhance our understanding of protein folding principles

Structural biology is traditionally an experimental science building on data collected by X-ray crystallography, and more recently, cryo-electron microscopy. Such data and the reconstructed structures provide a lens into the principles of protein folding, and help connect particular protein amino acid sequence, and corresponding solved protein structures. But, solved protein structures are snapshots of a … More Computational protein design provides insights that enhance our understanding of protein folding principles

Machine learning models are derived based on correlations rather than mechanistic insights

Machine learning tools have found utility in a variety of fields ranging from material synthesis to bioinformatics and medicine. However, little is known about how machine learning models are derived. Basically, machine learning models are obtained based on the work of pattern recognition algorithms gleaning unseen correlations between variables in a large dataset, the latter … More Machine learning models are derived based on correlations rather than mechanistic insights

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 could only output the predominant structure or the structure with the best signal to noise ratio

In recent years, cryo-electron microscopy has shown its fortitude in solving an array of increasingly difficult and more complex protein structures. But, is the technique capable of solving all possible conformations of a protein? The answer is no, as cryo-electron microscopy could only output the predominant structure or the structure with the best signal to … More Cryo-electron microscopy could only output the predominant structure or the structure with the best signal to noise ratio

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

Machine learning models are derived based on correlations rather than mechanistic insights

Machine learning tools have found utility in a variety of fields ranging from material synthesis to bioinformatics and medicine. However, little is known about how machine learning models are derived. Basically, machine learning models are obtained based on the work of pattern recognition algorithms gleaning unseen correlations between variables in a large dataset, the latter … More Machine learning models are derived based on correlations rather than mechanistic insights

Cheaper cryo-electron microscopes are needed to popularize the technique

Cryo-electron microscopy has emerged as the dominant technique for protein structural determination compared to X-ray crystallography due to its relative ease in sample preparation. Specifically, samples for cryo-electron microscopy investigation does not need to be crystallized, rather, snap-freezing in liquid ethane would transform the protein sample into a glassy matrix suitable for examination under the … More Cheaper cryo-electron microscopes are needed to popularize the technique

Cryo-electron microscopy is able to handle a larger subset of proteins compared to X-ray crystallography

Ability to image proteins in a frozen state without prior crystallization is one of the main attractions of cryo-electron microscopy. But, the method is also more accommodating to a large variety of proteins compared to the more traditional approach of X-ray crystallography. One example involves the structural elucidation of membrane proteins. In traditional X-ray crystallography, … More Cryo-electron microscopy is able to handle a larger subset of proteins compared to X-ray crystallography

Degeneracy in protein sequence meant that evolutionary conservation occurred at the structure level

Given the importance of many proteins to the maintenance of cellular processes, the structures of the proteins are highly conserved independent of the sequence information at the amino acid and nucleotide level. This raises an important question in evolutionary biology: the direction in which natural selection exerts its effect in selecting for specific information bits … More Degeneracy in protein sequence meant that evolutionary conservation occurred at the structure level