Abstract
This chapter deals with networks of various kinds, notably the network of protein–protein interactions and regulatory networks. The biophysicochemical aspects of the interactions, including specificity and cooperative binding, are discussed, followed by an account of the various in vivo and in vitro (including chromatography and biosensing) experimental methods that can be used to gather the primary data on interactions, from which interactomic inferences may follow.
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Notes
- 1.
Eukaryotic cells in particular are in a great deal more structured than the simple picture suggests: Filaments of various kinds (e.g., microtubules) appear to function inter alia as tracks along which certain molecules are transported to specific destinations. However, even in this case, the information-bearing (“signalling”) molecule has first to encounter, and bind to, the carrier molecule that will convey it along the track.
- 2.
McConkey has coined the term “quinary structure” (of proteins) for this web of interactions.
- 3.
This statement, the obvious corollary of the central dogma, is actually quite problematical—in the sense of having a rather ambiguous meaning—when scrutinized in detail. Many functionally relevant proteins are significantly modified (e.g., glycosylated) by enzymes after translation. Of course, these enzymes themselves are gene products.
- 4.
Many transcription factors, for example, are multiprotein complexes.
- 5.
Groups of operons controlled by a single transcription factor are called regulons; groups of regulons are called modulons.
- 6.
After VohradskĂ˝ (2001).
- 7.
Kitano (2002).
- 8.
Vu and VohradskĂ˝ (2007).
- 9.
In the literature, K is often loosely defined using Eq. (16.6) with concentrations rather than mole fractions, whereupon it loses its dimensionless quality.
- 10.
Remarkable specificity is achievable (see, e.g., Popescu and Misevic 1997).
- 11.
The dehydron (Sect. 11.5.2) is an underwrapped (i.e., underdesolvated) hydrogen bond and is a key determinant of protein affinity.
- 12.
- 13.
Hydrogen-bonding is a special example of Lewis acid–base (AB) or electron donor–acceptor (da) interactions.
- 14.
See Ramsden (2000).
- 15.
See, e.g., Kornyshev and Leikin (2001).
- 16.
- 17.
See Ramsden (1994) for a comprehensive survey of all these and others.
- 18.
Kozma et al. (2009).
- 19.
A popular way to avoid the bioincompatibility of the gold or silver surface of the transducer required with SPR has been to coat it with a thick (
nm) layer of a biocompatible polysaccharide such as dextran, which forms a hydrogel, to which the target protein is bound. Unfortunately, this drastically changes the transport properties of the solution in the vicinity of the target (bound) protein (see Schuck 1996), which can lead to errors
of up to several orders of magnitude in apparent binding constants (via a differential effect on \(k_\mathrm{a}\) and \(k_\mathrm{d}\)). Furthermore, such materials interact very strongly (via hydrogen bonds) with water, altering its hydrophilicity, with concomitant drastic changes to protein affinity, leading to further, possibly equally large, distortions in binding constant via its link to the free energy of interaction (\(\Delta G = -RT\ln K\)). - 20.
Section 14.5; the immobilization of proteins without altering their conformation, and hence association characteristics, is however more difficult than for nucleic acid oligomers.
- 21.
See also Sect. 14.1 for limitations of the technique.
- 22.
Jeong et al. (2001).
nm) layer of a biocompatible polysaccharide such as dextran, which forms a hydrogel, to which the target protein is bound. Unfortunately, this drastically changes the transport properties of the solution in the vicinity of the target (bound) protein (see Schuck References
Jeong H, Mason SP, Barabási A-L, Oltvai ZN (2001) Lethality and centrality in protein networks. Nature 411:41–42
Kitano H (2002) Systems biology: a brief overview. Science 295:1662–1664
Kornyshev AA, Leikin S (2001) Sequence recognition in the pairing of DNA duplexes. Phys Rev Lett 86:3666–3669
Kozma P, Hamori A, Cottier K, Kurunczi S, Horvath R (2009) Grating coupled interferometry for optical sensing. Appl Phys B 97:5–8
Popescu O, Misevic GN (1997) Self-recognition by proteoglycans. Nature 386:231–232
Ramsden JJ (1984) The photolysis of small silver halide particles. Proc R Soc Lond A 392:427–444
Ramsden JJ (1986) Computing photographic response curves. Proc R Soc Lond A 406:27–37
Ramsden JJ (1994) Experimental methods for investigating protein adsorption kinetics at surfaces. Q Rev Biophys 27:41–105
Ramsden JJ (2000) The specificity of biomolecular particle adhesion. Colloids Surf A 173:237–249
Ramsden JJ, Dreier J (1996) Kinetics of the interaction between DNA and the type IC restriction enzyme EcoR124/3I. Biochemistry 35:3746–3753
Ramsden JJ, Grätzel M (1986) Formation and decay of methyl viologen radical cation dimers on the surface of colloidal CdS. Chem Phys Lett 132:269–272
Scheller F, Schubert F (1989) Biosensoren. Berlin: Akademie-Verlag
Schuck P (1996) Kinetics of ligand binding to receptors immobilized in a polymer matrix, as detected with an evanescent wave biosensor. I. A computer simulation of the influence of mass transport. Biophys. J. 70 1230–1249
Vohradský J (2001) Neural network model of gene expression. FASEB J 15:846–854
Vu TT, Vohradský J (2007) Nonlinear differential equation model for quantification of transcriptional regulation applied to microarray data of Saccharomyces cerevisiae. Nucleic Acids Res 35:279–287
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Ramsden, J. (2015). Interactomics: Interactions and Regulatory Networks. In: Bioinformatics. Computational Biology, vol 21. Springer, London. https://doi.org/10.1007/978-1-4471-6702-0_16
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DOI: https://doi.org/10.1007/978-1-4471-6702-0_16
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