title: Defining network topologies that can achieve biochemical adaptation.
abstract: Many signaling systems show adaptation-the ability to reset themselves after responding to a stimulus. We computationally searched all possible three-node enzyme network topologies to identify those that could perform adaptation. Only two major core topologies emerge as robust solutions: a negative feedback loop with a buffering node and an incoherent feedforward loop with a proportioner node. Minimal circuits containing these topologies are, within proper regions of parameter space, sufficient to achieve adaptation. More complex circuits that robustly perform adaptation all contain at least one of these topologies at their core. This analysis yields a design table highlighting a finite set of adaptive circuits. Despite the diversity of possible biochemical networks, it may be common to find that only a finite set of core topologies can execute a particular function. These design rules provide a framework for functionally classifying complex natural networks and a manual for engineering networks. For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.
authors.affiliation: Center for Theoretical Biology, Peking University, Beijing 100871, China..
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ma
authors.forename: Ala
authors.initials: A
authors.lastname: Trusina
authors.forename: Hana
authors.initials: H
authors.lastname: El-Samad
authors.forename: Wendell A
authors.initials: WA
authors.lastname: Lim
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
mesh_terms: D000222:Adaptation, Physiological; D003198:Computer Simulation; D004798:Enzymes / Q000378:metabolism; D025461:Feedback, Physiological; D008954:Models, Biological; D015398:Signal Transduction
chemical_list: D004798:Enzymes
references.citation: J Physiol. 2001 Jan 1;530(Pt 1):113-22
references.pmid: 11136863
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13040-4
references.pmid: 16924119
references.citation: Nat Genet. 2002 May;31(1):64-8
references.pmid: 11967538
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8223-8
references.pmid: 12826616
references.citation: Science. 1999 Apr 30;284(5415):765-70
references.pmid: 10221901
references.citation: Mol Syst Biol. 2006;2:70
references.pmid: 17170765
references.citation: Science. 2005 Oct 21;310(5747):496-8
references.pmid: 16239477
references.citation: Science. 2008 Jan 25;319(5862):482-4
references.pmid: 18218902
references.citation: Science. 2002 Oct 25;298(5594):824-7
references.pmid: 12399590
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11775-80
references.pmid: 16087882
references.citation: Nature. 1997 Jun 26;387(6636):913-7
references.pmid: 9202124
references.citation: Phys Biol. 2008 Jun 24;5(2):026009
references.pmid: 18577806
references.citation: Syst Control Lett. 2006 Apr;55(4):329-337
references.pmid: 17401451
references.citation: Nature. 2005 Nov 24;438(7067):504-7
references.pmid: 16306993
references.citation: Biophys J. 2002 Jan;82(1 Pt 1):50-63
references.pmid: 11751295
references.citation: PLoS Biol. 2004 Feb;2(2):E49
references.pmid: 14966542
references.citation: J Biol Chem. 1993 Sep 5;268(25):18610-6
references.pmid: 8395512
references.citation: Science. 2008 Jul 4;321(5885):126-9
references.pmid: 18599789
references.citation: Nat Rev Genet. 2007 Jun;8(6):450-61
references.pmid: 17510665
references.citation: Biophys J. 2007 Aug 1;93(3):806-21
references.pmid: 17513354
references.citation: J Biol Chem. 1984 Dec 10;259(23):14441-7
references.pmid: 6501300
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4649-53
references.pmid: 10781070
references.citation: J Theor Biol. 2002 Jan 7;214(1):17-29
references.pmid: 11786029
references.citation: Nature. 1972 Oct 27;239(5374):500-4
references.pmid: 4563019
references.citation: Proc Natl Acad Sci U S A. 1972 Sep;69(9):2509-12
references.pmid: 4560688
references.citation: Curr Opin Neurobiol. 2003 Aug;13(4):469-75
references.pmid: 12965295
references.citation: PLoS Comput Biol. 2008 Jan;4(1):e8
references.pmid: 18179281