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Updated: Oct 18, 2025

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
AlphaFold 2: Why It Works and Its Implications for Understanding the Relationships of Protein Sequence, Structure,
Jeffrey Skolnick1, Mu Gao1, Hongyi Zhou1
1Center for the Study of Systems Biology, School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
Abstract:
AlphaFold 2 (AF2) was the star of CASP14, the last biannual structure prediction experiment. Using novel deep learning, AF2 predicted the structures of many difficult protein targets at or near experimental resolution. Here, we present our perspective of why AF2 works and show that it is a very sophisticated fold recognition algorithm that exploits the completeness of the library of single domain PDB structures. It has also learned local side chain packing rearrangements that enable it to refine proteins to high resolution. The benefits and limitations of its ability to predict the structures of many more proteins at or close to atomic detail are discussed.
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