Landmark papers in protein and peptide science

The discoveries every biochemistry student should know, with citations you can use.

1. 1913

   Michaelis and Menten describe enzyme kinetics

   Their rate equation is still the starting point for enzyme kinetics. An English translation was published in 2011.

   Johnson KA, Goody RS. The original Michaelis constant: translation of the 1913 Michaelis–Menten paper. Biochemistry. 2011;50:8264–8269. Read source

2. 1922

   Insulin is isolated and used to treat diabetes

   Banting, Best, Collip and Macleod purified insulin, turning type 1 diabetes from fatal to treatable. Nobel Prize 1923.

   The Nobel Prize in Physiology or Medicine 1923. Read source

3. 1951

   Pauling describes the α-helix

   Using bond geometry rather than direct imaging, Pauling, Corey and Branson predicted the α-helix and pleated sheet.

   Pauling L, Corey RB, Branson HR. The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain. PNAS. 1951;37:205–211. Read source

4. 1953

   The first peptide hormone is synthesized

   Vincent du Vigneaud synthesized oxytocin, proving peptide hormones could be made in the lab. Nobel Prize 1955.

   The Nobel Prize in Chemistry 1955. Read source

5. 1955

   Sanger sequences insulin

   Frederick Sanger determined insulin’s full amino acid sequence, proving proteins have a defined sequence. Nobel Prize 1958.

   The Nobel Prize in Chemistry 1958. Read source

6. 1958

   The first 3D protein structure

   Kendrew and colleagues solved the structure of myoglobin by X-ray crystallography.

   Kendrew JC, et al. A three-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature. 1958;181:662–666. Read source

7. 1963

   Solid-phase peptide synthesis

   Merrifield anchored growing chains to a resin, making peptide synthesis fast and automatable. Nobel Prize 1984.

   Merrifield RB. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc. 1963;85:2149–2154. Read source

8. 1973

   Sequence determines structure

   Anfinsen summarized the experiments showing that a protein’s sequence encodes its fold. Nobel Prize 1972.

   Anfinsen CB. Principles that govern the folding of protein chains. Science. 1973;181:223–230. Read source

9. 1977

   Hypothalamic peptide hormones discovered

   Guillemin and Schally identified peptide hormones from the brain, including GnRH and somatostatin. Nobel Prize 1977.

   The Nobel Prize in Physiology or Medicine 1977. Read source

10. 2002

    Mass spectrometry of large biomolecules

    Fenn and Tanaka developed ways to ionize proteins for mass spectrometry, now the standard for identifying peptides. Nobel Prize 2002.

    The Nobel Prize in Chemistry 2002. Read source

11. 2017

    Cryo-electron microscopy

    Dubochet, Frank and Henderson made it possible to image biomolecules in near-native states. Nobel Prize 2017.

    The Nobel Prize in Chemistry 2017. Read source

12. 2021

    AlphaFold predicts protein structures

    A deep-learning system predicted structures with accuracy often close to experiment, transforming structural biology.

    Jumper J, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596:583–589. Read source

13. 2024

    Nobel Prize for protein design and prediction

    David Baker for computational protein design; Demis Hassabis and John Jumper for protein structure prediction.

    The Nobel Prize in Chemistry 2024. Read source