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Structural Biology

(Photo Courtesy of University of Toronto, Canada)


- Overview

Structural biology is a branch of molecular biology, biochemistry and biophysics that deals with molecules of biological macromolecules (especially proteins, composed of amino acids, RNA or DNA, composed of nucleotides, membranes, composed of lipids) structure, how they acquire the structure they have, and how changes in their structure affect their function. 

This topic is of great interest to biologists because macromolecules perform most of the functions of cells, and they can only perform these functions by coiling into specific three-dimensional shapes. This structure, the "tertiary structure" of the molecule, depends in complex ways on the basic composition or "primary structure" of each molecule.


- The Principle Methods Used in Structural Biology 

Biomolecules are too small to see details even with the most advanced light microscopes. The methods that structural biologists use to determine their structures often involve measuring large numbers of identical molecules simultaneously. These methods include:  

  • Mass spectrometry
  • Macromolecular crystallography
  • Neutron diffraction
  • Proteolysis
  • Nuclear magnetic resonance spectroscopy of proteins (NMR)
  • Electron paramagnetic resonance (EPR)
  • Cryogenic Electron Microscopy (cryoEM)
  • Electron crystallography and Microcrystal electron diffraction
  • Multiangle light scattering
  • Small angle scattering
  • Ultrafast laser spectroscopy
  • Dual-polarization interferometry and circular dichroism

Mostly, researchers use them to study the "native state" of macromolecules. But variants of these methods are also used to watch nascent or denatured molecules take on or re-take their native state. See protein folding.


- Structural Bioinformatics

A third approach that structural biologists use to understand structure is bioinformatics, which looks for patterns in the different sequences that give rise to specific shapes. Researchers can often infer aspects of intact membrane protein structure from membrane topology predicted by hydrophobicity analysis. 

Over the past few years, high-precision physical molecular models have become possible to complement computational studies of biological structures. Examples of these models can be found in the Protein Data Bank. 

Computational techniques such as molecular dynamics simulations can be used in conjunction with empirical structure determination strategies to extend and study protein structure, conformation, and function.


[More to come ...]


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