Category: structural biology

Enzyme activity prediction still revolves around the enzyme activity-protein structure correlate

March 29, 2024

From the theoretical perspective, enzyme structure is perhaps the easiest correlate for enzyme activity levels given the intuitive nature of structure-function correlates. But, the challenge lies in extracting useful features from a structural depiction that could be correlated with enzyme activity. To this end, the field of enzyme activity prediction still awaits comprehensive proteome level … More Enzyme activity prediction still revolves around the enzyme activity-protein structure correlate

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

March 18, 2024

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

February 10, 2024

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

February 1, 2024

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

January 24, 2024

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

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

January 22, 2024

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

January 9, 2024

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

Advanced image processing and storage solutions are needed to realise high temporal resolution imaging cum spectroscopy experiments in biology

December 12, 2023

Structural biology studies have been predominantly served by snapshots of protein in action such as during enzyme catalysis. Such snapshots in time have helped us elucidate important aspects of protein function. However, limitations in computational power have limited our ability to reconstruct long time series movies of protein in action. Advent in high performance computing … More Advanced image processing and storage solutions are needed to realise high temporal resolution imaging cum spectroscopy experiments in biology

Functional properties of proteins do not easily emanate from their structural model

November 20, 2023

Structure defines functions in biology, and this is the reason why obtaining a structural model of a protein is the first step in understanding its function. However, in some cases, functional properties of a protein are not easily discernible from its structural features without other ancillary assays or tests. To understand the problem, it is … More Functional properties of proteins do not easily emanate from their structural model

One obstacle in drug development is in the types of questions that could be asked in the lab and the clinic

September 14, 2023

Drug development is typically an expensive process that takes at least a decade or more. From an initial observation in the lab to a final product ready to be prescribed in the clinic, multiple skills set and questions need to be asked and addressed, and this explains the difficulty of the process. Specifically, questions asked … More One obstacle in drug development is in the types of questions that could be asked in the lab and the clinic