Traditionally...    How 3D-folded Protein Shapes were Determined included:

A. X-Ray Diffraction (Crystallography): - a beam of incident X-rays passed thru a crystal diffracts in many specific directions. By measuring the angles and intensities of these diffracted beams, a crystallographer can produce a three-dimensional picture of the density within the crystal.
                             
B. Cryo-Electron Microcopy (C-TEM): - samples are cooled to cryogenic temperatures and embedded in an environment of vitreous water (amorphous solid [non-crystalline] form of water produced by rapid cooling. Narrow e-beams capture each electron in TEM and software algorithms are used for the determination of biomolecular structures at near-atomic resolution.
     but now -next              














 
 C. Artificial Intelligence Computer Software Modeling:

     
A UK based artificial intelligence company [DeepMind Technologies] was acquired by Google in 2014. Google used it to create artificial intelligence software (Alpha Fold) that solves protein folding structures akin to those by X-ray crystallaography and cryo-electron microscopy.

     In a biennial protein-structure prediction challenge called CASP, short for Critical Assessment of Structure Prediction, AlphaFold out performed some 100 other AI software teams at the 2020 CASP.
 
     AlphaFold’s structure predictions were indistinguishable from those determined the ‘gold standard’  methods of X-ray crystallography and cryo-electron microscopy [click on figure below].
AlphaFold might lessen the need for these laborious and expensive methods and AI will make it possible to study living things in new ways. AlphaFold Uses the physical and geometric constraints that determine how a protein folds and comes up with a ‘consensus’ model of what the protein should look like.
     Some applications, such as the evolutionary analysis of proteins, are set to flourish because the tsunami of available genomic data might now be reliably translated into structures.
                                                  <-- click for animation 
                                  a protein's function is determined by its 3D shape
      BACK