Bioscience Engineering (Biological Engineering)

  • Richard Dods


This chapter (Bioscience Engineering) begins with a description of the emerging field of bioscience engineering (biological engineering). The chapter continues with a description of the relationship of amino acid sequence and the three-dimensional structure of proteins. This topic will be the central concept for the students’ introduction to bioscience engineering (bioengineering) and its importance will become evident as the reader proceeds in reading the book. The chapter describes the earliest technique used for protein folding, X-ray diffraction crystallography. X-ray diffraction crystallography was the first technique used to visualize and eventually classify proteins. The genetic code and alternative splicing are reviewed. Collections of proteins and their structures are described in this chapter. They include The Human Genome Project, The Protein Data Bank, and the Human Proteome Project. The earliest theory for how proteins fold, Anfinsen’s thermodynamic hypothesis, and its dependence on Gibbs free energy are presented.



Alternative splicing

Occurs when splicing of pre-mRNA to form mRNA results in more than one protein due to differential splicing.

Genetic code

Is the code used by which the mRNA sequence determines the amino acid sequence of a protein at the ribosome.

Gibbs free energy

Is the driving force of a reaction. A spontaneous reaction occurs if the free energy is negative and does not occur if it is positive.

Human Genome Project

Has sequenced the entire euchromatic DNA of humans.

Human Proteome Project

Maps the entire number of human proteins.

Isomorphic replacement

Involves the reaction of the protein with heavy elements. Crystallography results in a protein heavy metal crystal which supplies X-ray diffraction pictures which are easier to analyze.

Molecular replacement

Uses a protein of known three-dimensional structure to solve the conformation of a related protein.

Native proteins (denaturation/renaturation/coagulation)

Are proteins that conduct their function. If exposed to certain chemicals or heat, the proteins become nonfunctional and thereby are denatured. Removal of the denaturation agent restores them to their proper function (renaturation). Denaturation represents unfolding of the protein. If the protein once denatured cannot be restored to its normal function, it is said to be coagulated.

Protein Data Bank (PDB)

Is a worldwide depository of proteins.

Recognition sites

Are protein regions that bind molecules. The type of recognition site determines the classification of the protein as immunoglobulin, enzyme, structural, transport, or hormone.


Is the degree of “fuzziness” of the X-ray diffraction pattern. In modern times most X-ray diffraction patterns use 2 Å of resolution.

X-ray crystallography

Uses X-rays to strike a protein thus producing diffracted secondary waves which are used to ascertain the three-dimensional structure of the protein usually with the help of the amino acid sequence.

Further Reading

  1. Dods RF (1963) Pathophysiology for chemists. P.68. Audiocassette course. American Chemical Society. Washington, DC.Google Scholar
  2. Mirsky AE, Pauling L(1936) On the structure of native, denatured, and coagulated proteins. PNAS 22:439.CrossRefGoogle Scholar
  3. Anson ML (1945) Protein denaturation and the properties of protein groups. In Advances in Protein Chemistry, vol 2 Elsevier Inc. p. 361Google Scholar
  4. Sanger F, Tuppy H (1951} The amino-acid sequence in the phenylalanyl chain of insulin: 1. the identification of lower peptides from partial hydrolysates. Biochem J 49:463.Google Scholar
  5. Sanger F, Tuppy H (1951) The amino-acid sequence in the phenylalanyl chain of insulin. 2. The investigation of peptides from hydrolysates. Biochem J 49:31.Google Scholar
  6. Edman P (1950) Method for determination of the amino acid sequence in peptides. Acta Chem Scand 4:283.CrossRefGoogle Scholar
  7. Edman P, Begg G (1967) A protein sequenator. Eur J Biochem 1:80.CrossRefGoogle Scholar
  8. Bragg L, Perutz MF (1952) The structure of haemoglobin. Pro Royal Soc A 213:425.Google Scholar
  9. Green DW, Ingram VM, Perutz MF (1954) The structure of haemoglobin IV. Sign determination by the isomorphous replacement method. Proc Royal Soc A 225:19. doi: Scholar
  10. Kendrew JC, Bodo G, Dintzis HM, et al (1958) A three-dimensional model of the myoglobin molecule obtained by x-ray analysis. Nature 181:662.CrossRefGoogle Scholar
  11. Rossmann MG, Blow DM (1962) The detection of subunits within the crystallographic asymmetric unit. Acta Cryst. 15:24.CrossRefGoogle Scholar
  12. Caspar DLD, Klug A (1962) Physical principles in the construction of regular viruses. Cold Spring Harbor Symposia on Quantitative Biology 27:1.CrossRefGoogle Scholar
  13. Klug A (1982) From macromolecules to biological assemblies. Assessed 6/14/2017.
  14. Phillips DC (1967) The hen egg-white lysozyme molecule. PNAS 57:484.CrossRefGoogle Scholar
  15. Avey HP, Boles MO, Carlisle S, et al. (1967) Structure of ribonuclease. Nature 213:557.CrossRefGoogle Scholar
  16. Kartha G, Bello J, Harker D (1967) Tertiary structure of ribonuclease. Nature 213:862.CrossRefGoogle Scholar
  17. Dickerson RE, Kopka ML, Borders Jr CL, et al(1967) A centrosymmetric projection at 4 Å horse heart oxidized cytochrome c. J Mol Bio 29:77.CrossRefGoogle Scholar
  18. Dickerson RE, Kopka ML, Weinzierl J, et al (1967) Location of the heme in horse heart ferricytochrome c by x-ray diffraction. J Biol Chem 242:3015.Google Scholar
  19. Ludwig ML, Hartsuck JA, Steitz A, et al (1967) The structure of carboxypeptidase a. IV. Preliminary results at 2. Å resolution, and a substrate complex at 6 Å resolution. PNAS 57:511.CrossRefGoogle Scholar
  20. Edelman GM, Cunningham BA, Gall WE, et al (1969) The covalent structure of an entire λg immunoglobulin molecule. PNAS 63:78.CrossRefGoogle Scholar
  21. Poljak RJ, Amzel LM, Avey HP, et al (1973) Three-dimensional structure of the Fab’ fragment of a human immunoglobulin at 2.8-Å resolution. PNAS 70:3305.CrossRefGoogle Scholar
  22. Poljak RJ, Amzel LM, Chen BL, et al (1974) The three-dimensional structure of the Fab’ fragment of a human myeloma immunoglobulin at 2.0-Å resolution. PNAS 71:3440.CrossRefGoogle Scholar
  23. Pennisi E (2015) Of mice and men. Science 349:21.CrossRefGoogle Scholar
  24. Wilson BJ, Nicholls SG (2015) The human genome project, and recent advances in personalized genomics. Risk Management and Healthcare Policy 8:9.CrossRefGoogle Scholar
  25. Omenn GS (2017) Advances of the HUPO Human Proteome Project with broad applications for life sciences research. Expert Review of Proteomics 14:109.CrossRefGoogle Scholar
  26. Kim MS, Pinto SM, Getnet D, et al. (2014) A draft map of the human proteasome. Nature 14:509:575.CrossRefGoogle Scholar
  27. Chow LT, Gelinas RE, Broker TR, et al. (1977) An amazing sequence arrangement at the 5’ ends of adenovirus 2 messenger RNA. Cell 12:1. doi: Scholar
  28. Nobel Lectures in Chemistry, vol 5 (1971-1980) World Scientific Publishing Company, Inc. 1994.Google Scholar
  29. Anfinsen CB (1973) Principles that govern the folding of protein chains. Science 181:223.CrossRefGoogle Scholar
  30. Zwanzig, Attila S, Bagchi B. (1992) Levinthal’s paradox. PNAS 89:20CrossRefGoogle Scholar
  31. Holtkamp W, Kokic G, Jäger M, et. al (2015) Cotranslational protein folding on the ribosome monitored in real time. Science 350; 1104.CrossRefGoogle Scholar
  32. Pauweis K, Van Molie A, Tommassen J, et. al (2007) Chaperoning Anfinsen: the steric foldases. Mol. Microbiology 64; 917.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Richard Dods
    • 1
  1. 1.Illinois Mathematics and Science AcademyPalatineUSA

Personalised recommendations