Allosteric regulation of proteins continues to be an engaging research topic for the scientific community. Models describing allosteric communication have evolved from focusing on conformation-based descriptors of protein structural changes to appreciating the role of internal protein dynamics as a mediator of allostery. Here, we explain a “violin model” for allostery as a contemporary method for approaching the Cooper–Dryden model based on redistribution of protein thermal fluctuations. Based on graph theory, the violin model makes use of community network analysis to functionally cluster correlated protein motions obtained from molecular dynamics simulations. This Review provides the theory and workflow of the methodology and explains the application of violin model to unravel the workings of protein kinase A.
REFERENCES
1.
S. S.
Taylor
, M. M.
Keshwani
, J. M.
Steichen
, and A. P.
Kornev
, “Evolution of the eukaryotic protein kinases as dynamic molecular switches
,” Philos. Trans. R. Soc., B
367
(1602
), 2517
–2528
(2012
).2.
R.
Nussinov
and C.-J.
Tsai
, “Allostery in disease and in drug discovery
,” Cell
153
(2
), 293
–305
(2013
).3.
L. G.
Ahuja
, A. P.
Kornev
, C. L.
McClendon
, G.
Veglia
, and S. S.
Taylor
, “Mutation of a kinase allosteric node uncouples dynamics linked to phosphotransfer
,” Proc. Natl. Acad. Sci. U. S. A.
114
(6
), E931
–E940
(2017
).4.
N.
Jura
, X.
Zhang
, N. F.
Endres
, M. A.
Seeliger
, T.
Schindler
, and J.
Kuriyan
, “Catalytic control in the EGF receptor and its connection to general kinase regulatory mechanisms
,” Mol. Cell
42
(1
), 9
–22
(2011
).5.
W. W. A.
Schamel
, B.
Alarcon
, T.
Höfer
, and S.
Minguet
, “The allostery model of TCR regulation
,” J. Immunol.
198
(1
), 47
–52
(2017
).6.
A. W.
Fenton
, “Allostery: An illustrated definition for the ‘second secret of life’
,”. Trends Biochem. Sci.
33
(9
), 420
–425
(2008
).7.
J.-P.
Changeux
, “Allostery and the Monod-Wyman-Changeux model after 50 years
,” Annu. Rev. Biophys.
41
, 103
–133
(2012
).8.
S. J.
Wodak
, E.
Paci
, N. V.
Dokholyan
, I. N.
Berezovsky
, A.
Horovitz
, J.
Li
, V. J.
Hilser
, I.
Bahar
, J.
Karanicolas
, G.
Stock
, P.
Hamm
, R. H.
Stote
, J.
Eberhardt
, Y.
Chebaro
, A.
Dejaegere
, M.
Cecchini
, J. P.
Changeux
, P. G.
Bolhuis
, J.
Vreede
, P.
Faccioli
, S.
Orioli
, R.
Ravasio
, L.
Yan
, C.
Brito
, M.
Wyart
, P.
Gkeka
, I.
Rivalta
, G.
Palermo
, J. A.
McCammon
, J.
Panecka-Hofman
, R. C.
Wade
, A.
Di Pizio
, M. Y.
Niv
, R.
Nussinov
, C. J.
Tsai
, H.
Jang
, D.
Padhorny
, D.
Kozakov
, and T.
McLeish
, “Allostery in its many disguises: From theory to applications
,” Structure
27
, 566
(2019
).9.
J.
Monod
, J.
Wyman
, and J.-P.
Changeux
, “On the nature of allosteric transitions: A plausible model
,” J. Mol. Biol.
12
, 88
–118
(1965
).10.
D. E.
Koshland
, Jr., G.
Némethy
, and D.
Filmer
, “Comparison of experimental binding data and theoretical models in proteins containing subunits
,” Biochemistry
5
(1
), 365
–385
(1966
).11.
W. A.
Eaton
, E. R.
Henry
, J.
Hofrichter
, and A.
Mozzarelli
, “Is cooperative oxygen binding by hemoglobin really understood?
,” Nat. Struct. Biol.
6
(4
), 351
–358
(1999
).12.
W. A.
Eaton
, E. R.
Henry
, J.
Hofrichter
, S.
Bettati
, C.
Viappiani
, and A.
Mozzarelli
, “Evolution of allosteric models for hemoglobin
,” IUBMB Life
59
(8–9
), 586
–599
(2007
).13.
E. R.
Henry
, S.
Bettati
, J.
Hofrichter
, and W. A.
Eaton
, “A tertiary two-state allosteric model for hemoglobin
,” Biophys. Chem.
98
(1–2
), 149
–164
(2002
).14.
G. D.
Reinhart
, “Quantitative analysis and interpretation of allosteric behavior
,” Methods Enzymol.
380
, 187
–203
(2004
).15.
P.
Purohit
, A.
Mitra
, and A.
Auerbach
, “A stepwise mechanism for acetylcholine receptor channel gating
,” Nature
446
(7138
), 930
–933
(2007
).16.
A.
Velyvis
, H. K.
Schachman
, and L. E.
Kay
, “Application of methyl-TROSY NMR to test allosteric models describing effects of nucleotide binding to aspartate transcarbamoylase
,” J. Mol. Biol.
387
(3
), 540
–547
(2009
).17.
M. J.
Whitley
and A. L.
Lee
, “Frameworks for understanding long-range intra-protein communication
,” Curr. Protein Pept. Sci.
10
(2
), 116
–127
(2009
).18.
E. W.
Yu
and D. E.
Koshland
, Jr., “Propagating conformational changes over long (and short) distances in proteins
,” Proc. Natl. Acad. Sci. U. S. A.
98
(17
), 9517
–9520
(2001
).19.
V. J.
Hilser
, J. O.
Wrabl
, and H. N.
Motlagh
, “Structural and energetic basis of allostery
,” Annu. Rev. Biophys.
41
, 585
–609
(2012
).20.
R. A.
Laskowski
, F.
Gerick
, and J. M.
Thornton
, “The structural basis of allosteric regulation in proteins
,” FEBS Lett.
583
(11
), 1692
–1698
(2009
).21.
H.
Prinz
, “Hill coefficients, dose-response curves and allosteric mechanisms
,” J. Chem. Biol.
3
(1
), 37
–44
(2010
).22.
U.
Haupts
, J.
Tittor
, and D.
Oesterhelt
, “Closing in on bacteriorhodopsin: Progress in understanding the molecule
,” Annu. Rev. Biophys. Biomol. Struct.
28
, 367
–399
(1999
).23.
M. J.
Tyska
and D. M.
Warshaw
, “The myosin power stroke
,” Cell Motil. Cytoskeleton
51
(1
), 1
–15
(2002
).24.
J. L.
England
, “Allostery in protein domains reflects a balance of steric and hydrophobic effects
,” Structure
19
(7
), 967
–975
(2011
).25.
R.
Elber
, “Simulations of allosteric transitions
,” Curr. Opin. Struct. Biol.
21
(2
), 167
–172
(2011
).26.
D.
Kern
and E. R.
Zuiderweg
, “The role of dynamics in allosteric regulation
,” Curr. Opin. Struct. Biol.
13
(6
), 748
–757
(2003
).27.
C.-J.
Tsai
, A.
del Sol
, and R.
Nussinov
, “Allostery: Absence of a change in shape does not imply that allostery is not at play
,” J. Mol. Biol.
378
(1
), 1
–11
(2008
).28.
J.
Xie
and L.
Lai
, “Protein topology and allostery
,” Curr. Opin. Struct. Biol.
62
, 158
–165
(2020
).29.
G.
Kar
, O.
Keskin
, A.
Gursoy
, and R.
Nussinov
, “Allostery and population shift in drug discovery
,” Curr. Opin. Pharmacol.
10
(6
), 715
–722
(2010
).30.
B.
Ma
, M.
Shatsky
, H. J.
Wolfson
, and R.
Nussinov
, “Multiple diverse ligands binding at a single protein site: A matter of pre-existing populations
,” Protein Sci.
11
(2
), 184
–197
(2002
).31.
Q.
Cui
and M.
Karplus
, “Allostery and cooperativity revisited
,” Protein Sci.
17
(8
), 1295
–1307
(2008
).32.
H. N.
Motlagh
, J. O.
Wrabl
, J.
Li
, and V. J.
Hilser
, “The ensemble nature of allostery
,” Nature
508
(7496
), 331
–339
(2014
).33.
R.
Nussinov
, “Introduction to protein ensembles and allostery
,” Chem. Rev.
116
(11
), 6263
–6266
(2016
).34.
S.-R.
Tzeng
and C. G.
Kalodimos
, “Allosteric inhibition through suppression of transient conformational states
,” Nat. Chem. Biol.
9
(7
), 462
–465
(2013
).35.
T.
Saleh
, P.
Rossi
, and C. G.
Kalodimos
, “Atomic view of the energy landscape in the allosteric regulation of Abl kinase
,” Nat. Struct. Mol. Biol.
24
(11
), 893
–901
(2017
).36.
B.
Wright
, K. A.
Watson
, L. J.
McGuffin
, J. A.
Lovegrove
, and J. M.
Gibbins
, “GRID and docking analyses reveal a molecular basis for flavonoid inhibition of Src family kinase activity
,” J. Nutr. Biochem.
26
(11
), 1156
–1165
(2015
).37.
U.
Derewenda
, M.
Artamonov
, G.
Szukalska
, D.
Utepbergenov
, N.
Olekhnovich
, H. I.
Parikh
, G. E.
Kellogg
, A. V.
Somlyo
, and Z. S.
Derewenda
, “Identification of quercitrin as an inhibitor of the p90 S6 ribosomal kinase (RSK): Structure of its complex with the N-terminal domain of RSK2 at 1.8 Å resolution
,” Acta Crystallogr., Sect. D: Biol. Crystallogr.
69
(Pt 2
), 266
–275
(2013
).38.
N.
Popovych
, S.
Sun
, R. H.
Ebright
, and C. G.
Kalodimos
, “Dynamically driven protein allostery
,” Nat. Struct. Mol. Biol.
13
(9
), 831
–838
(2006
).39.
R.
Nussinov
and C.-J.
Tsai
, “Allostery without a conformational change? Revisiting the paradigm
,” Curr. Opin. Struct. Biol.
30
, 17
–24
(2015
).40.
T. P.
Schrank
, D. W.
Bolen
, and V. J.
Hilser
, “Rational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins
,” Proc. Natl. Acad. Sci. U. S. A.
106
(40
), 16984
–16989
(2009
).41.
S. E.
Reichheld
, Z.
Yu
, and A. R.
Davidson
, “The induction of folding cooperativity by ligand binding drives the allosteric response of tetracycline repressor
,” Proc. Natl. Acad. Sci. U. S. A.
106
(52
), 22263
–22268
(2009
).42.
T.
Hol
, M. B.
Cox
, H. U.
Bryant
, and M. W.
Draper
, “Selective estrogen receptor modulators and postmenopausal women’s health
,” J. Women’s Health
6
(5
), 523
–531
(1997
).43.
B. S.
Katzenellenbogen
, M. M.
Montano
, K.
Ekena
, M. E.
Herman
, and E. M.
McInerney
, “William L. McGuire memorial lecture. Antiestrogens: Mechanisms of action and resistance in breast cancer
,” Breast Cancer Res. Treat.
44
(1
), 23
–38
(1997
).44.
L. G.
Ahuja
, S. S.
Taylor
, and A. P.
Kornev
, “Tuning the `violin' of protein kinases: The role of dynamics-based allostery
,” IUBMB Life
71
(6
), 685
–696
(2019
).45.
A.
Cooper
and D. T. F.
Dryden
, “Allostery without conformational change. A plausible model
,” Eur Biophys J
11
(2
), 103
–109
(1984
).46.
A. L.
Lee
, S. A.
Kinnear
, and A. J.
Wand
, “Redistribution and loss of side chain entropy upon formation of a calmodulin-peptide complex
,” Nat. Struct. Biol.
7
(1
), 72
–77
(2000
).47.
A. P.
Kornev
, “Self-organization, entropy and allostery
,” Biochem. Soc. Trans.
46
(3
), 587
–597
(2018
).48.
I.
Bahar
, T. R.
Lezon
, L.-W.
Yang
, and E.
Eyal
, “Global dynamics of proteins: Bridging between structure and function
,” Annu. Rev. Biophys.
39
, 23
–42
(2010
).49.
L.
Zhang
, S.
Bouguet-Bonnet
, and M.
Buck
, “Combining NMR and molecular dynamics studies for insights into the allostery of small GTPase-protein interactions
,” Methods Mol. Biol.
796
, 235
–259
(2012
).50.
K. W.
East
, E.
Skeens
, J. Y.
Cui
, H. B.
Belato
, B.
Mitchell
, R.
Hsu
, V. S.
Batista
, G.
Palermo
, and G. P.
Lisi
, “NMR and computational methods for molecular resolution of allosteric pathways in enzyme complexes
,” Biophys. Rev.
12
(1
), 155
–174
(2020
).51.
J.
Kim
, L. G.
Ahuja
, F. A.
Chao
, Y.
Xia
, C. L.
McClendon
, A. P.
Kornev
, S. S.
Taylor
, and G.
Veglia
, “A dynamic hydrophobic core orchestrates allostery in protein kinases
,” Sci. Adv.
3
(4
), e1600663
(2017
).52.
C. M.
Petit
, J.
Zhang
, P. J.
Sapienza
, E. J.
Fuentes
, and A. L.
Lee
, “Hidden dynamic allostery in a PDZ domain
,” Proc. Natl. Acad. Sci. U. S. A.
106
(43
), 18249
–18254
(2009
).53.
L. G.
Ahuja
, P. C.
Aoto
, A. P.
Kornev
, G.
Veglia
, and S. S.
Taylor
, “Dynamic allostery-based molecular workings of kinase:peptide complexes
,” Proc. Natl. Acad. Sci. U. S. A.
116
(30
), 15052
–15061
(2019
).54.
S. S.
Taylor
, J.
Wu
, J. G. H.
Bruystens
, J. C.
Del Rio
, T.-W.
Lu
, A. P.
Kornev
, and L. F.
Ten Eyck
, “From structure to the dynamic regulation of a molecular switch: A journey over 3 decades
,” J. Biol. Chem.
296
, 100746
(2021
).55.
C. L.
McClendon
, A. P.
Kornev
, M. K.
Gilson
, and S. S.
Taylor
, “Dynamic architecture of a protein kinase
,” Proc. Natl. Acad. Sci. U. S. A
111
(43
), E4623
–E4631
(2014
).56.
A. P.
Kornev
and S. S.
Taylor
, “Dynamics-driven allostery in protein kinases
,” Trends Biochem. Sci.
40
(11
), 628
–647
(2015
).57.
A. P.
Kornev
, P. C.
Aoto
, and S. S.
Taylor
, “Calculation of centralities in protein kinase A
,” Proc. Natl. Acad. Sci. U. S. A.
119
(47
), e2215420119
(2022
).58.
M.
French
and G.
Bissinger
, “Testing of acoustic stringed musical instruments—An introduction
,” Exp. Tech.
25
(1
), 40
–43
(2001
).59.
M.
Fleming
, C. M.
Hutchins
, and V.
Benade
, “Research papers in violin acoustics 1975–1993
,” Galpin Soc. J.
51
, 221
(1998
).60.
C.
Gough
, “The violin: Chladni patterns, plates, shells and sounds
,” Eur. Phys. J. Spec. Top.
145
(1
), 77
–101
(2007
).61.
J.
Woodhouse
, “The physics of the violin
,” Contemp. Phys.
27
, 61
–62
(1986
).62.
C. E.
Gough
, “A violin shell model: Vibrational modes and acoustics
,” J. Acoust. Soc. Am.
137
(3
), 1210
–1225
(2015
).63.
M. M.
Tirion
, “Large amplitude elastic motions in proteins from a single-parameter, atomic analysis
,” Phys. Rev. Lett.
77
(9
), 1905
–1908
(1996
).64.
Y.
Togashi
and H.
Flechsig
, “Coarse-grained protein dynamics studies using elastic network models
,” Int. J. Mol. Sci.
19
(12
), 3899
(2018
).65.
A. R.
Atilgan
, S. R.
Durell
, R. L.
Jernigan
, M. C.
Demirel
, O.
Keskin
, and I.
Bahar
, “Anisotropy of fluctuation dynamics of proteins with an elastic network model
,” Biophys. J.
80
(1
), 505
–515
(2001
).66.
I.
Dubanevics
and T. C. B.
McLeish
, “Optimising elastic network models for protein dynamics and allostery: Spatial and modal cut-offs and backbone stiffness
,” J. Mol. Biol.
434
(17
), 167696
(2022
).67.
F.
Radicchi
, C.
Castellano
, F.
Cecconi
, V.
Loreto
, and D.
Parisi
, “Defining and identifying communities in networks
,” Proc. Natl. Acad. Sci. U. S. A.
101
(9
), 2658
–2663
(2004
).68.
I.
Rivalta
and V. S.
Batista
, “Community network analysis of allosteric proteins
,” Methods Mol. Biol.
2253
, 137
–151
(2021
).69.
S.
Essiz
and R. D.
Coalson
, “A rigid-body Newtonian propagation scheme based on instantaneous decomposition into rotation and translation blocks
,” J. Chem. Phys.
124
(14
), 144116
(2006
).70.
I.
Bahar
, A. R.
Atilgan
, and B.
Erman
, “Direct evaluation of thermal fluctuations in proteins using a single-parameter harmonic potential
,” Folding Des.
2
(3
), 173
–181
(1997
).71.
K.
Hinsen
, “Analysis of domain motions by approximate normal mode calculations
,” Proteins
33
(3
), 417
–429
(1998
).72.
C.
Atilgan
, Z. N.
Gerek
, S. B.
Ozkan
, and A. R.
Atilgan
, “Manipulation of conformational change in proteins by single-residue perturbations
,” Biophys. J.
99
(3
), 933
–943
(2010
).73.
V.
Alexandrov
, U.
Lehnert
, N.
Echols
, D.
Milburn
, D.
Engelman
, and M.
Gerstein
, “Normal modes for predicting protein motions: A comprehensive database assessment and associated web tool
,” Protein Sci.
14
(3
), 633
–643
(2005
).74.
N.
Go
, T.
Noguti
, and T.
Nishikawa
, “Dynamics of a small globular protein in terms of low-frequency vibrational modes
,” Proc. Natl. Acad. Sci. U. S. A.
80
(12
), 3696
–3700
(1983
).75.
B.
Brooks
and M.
Karplus
, “Normal modes for specific motions of macromolecules: Application to the hinge-bending mode of lysozyme
,” Proc. Natl. Acad. Sci. U. S. A.
82
(15
), 4995
–4999
(1985
).76.
A.
Kitao
, F.
Hirata
, and N.
Gō
, “The effects of solvent on the conformation and the collective motions of protein: Normal mode analysis and molecular dynamics simulations of melittin in water and in vacuum
,” Chem. Phys.
158
(2–3
), 447
–472
(1991
).77.
P.
Doruker
, A. R.
Atilgan
, and I.
Bahar
, “Dynamics of proteins predicted by molecular dynamics simulations and analytical approaches: Application to alpha-amylase inhibitor
,” Proteins
40
(3
), 512
–524
(2000
).78.
W.
Zheng
, B.
Brooks
, and D.
Thirumalai
, “Allosteric transitions in biological nanomachines are described by robust normal modes of elastic networks
,” Curr. Protein Pept. Sci.
10
(2
), 128
–132
(2009
).79.
H.
Flechsig
and Y.
Togashi
, “Designed elastic networks: Models of complex protein machinery
,” Int. J. Mol. Sci.
19
(10
), 3152
(2018
).80.
D.
Ming
and M. E.
Wall
, “Quantifying allosteric effects in proteins
,” Proteins
59
(4
), 697
–707
(2005
).81.
C.
Atilgan
and A. R.
Atilgan
, “Perturbation-response scanning reveals ligand entry-exit mechanisms of ferric binding protein
,” PLoS Comput. Biol.
5
(10
), e1000544
(2009
).82.
B.
Erman
, “A fast approximate method of identifying paths of allosteric communication in proteins
,” Proteins
81
(7
), 1097
–1101
(2013
).83.
P.
Guzel
and O.
Kurkcuoglu
, “Identification of potential allosteric communication pathways between functional sites of the bacterial ribosome by graph and elastic network models
,” Biochim. Biophys. Acta, Gen. Subj.
1861
(12
), 3131
–3141
(2017
).84.
J. G.
Su
, L. S.
Qi
, C. H.
Li
, Y. Y.
Zhu
, H. J.
Du
, Y. X.
Hou
, R.
Hao
, and J. H.
Wang
, “Prediction of allosteric sites on protein surfaces with an elastic-network-model-based thermodynamic method
,” Phys. Rev. E
90
(2
), 022719
(2014
).85.
X.-Q.
Yao
, L.
Skjærven
, and B. J.
Grant
, “Rapid characterization of allosteric networks with ensemble normal mode analysis
,” J. Phys. Chem. B
120
(33
), 8276
–8288
(2016
).86.
M.
Tekpinar
and A.
Yildirim
, “Only a subset of normal modes is sufficient to identify linear correlations in proteins
,” J. Chem. Inf. Model.
58
(9
), 1947
–1961
(2018
).87.
88.
M.
Girvan
and M. E. J.
Newman
, “Community structure in social and biological networks
,” Proc. Natl. Acad. Sci. U. S. A.
99
(12
), 7821
–7826
(2002
).89.
R. A.
Estabrook
, J.
Luo
, M. M.
Purdy
, V.
Sharma
, P.
Weakliem
, T. C.
Bruice
, and N. O.
Reich
, “Statistical coevolution analysis and molecular dynamics: Identification of amino acid pairs essential for catalysis
,” Proc. Natl. Acad. Sci. U. S. A.
102
(4
), 994
–999
(2005
).90.
C. L.
McClendon
, G.
Friedland
, D. L.
Mobley
, H.
Amirkhani
, and M. P.
Jacobson
, “Quantifying correlations between allosteric sites in thermodynamic ensembles
,” J. Chem. Theory Comput.
5
(9
), 2486
–2502
(2009
).91.
T.
Ichiye
and M.
Karplus
, “Collective motions in proteins: A covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations
,” Proteins
11
(3
), 205
–217
(1991
).92.
A.
Sethi
, J.
Eargle
, A. A.
Black
, and Z.
Luthey-Schulten
, “Dynamical networks in tRNA:protein complexes
,” Proc. Natl. Acad. Sci. U. S. A.
106
(16
), 6620
–6625
(2009
).93.
B. J.
Killian
, J.
Yundenfreund Kravitz
, and M. K.
Gilson
, “Extraction of configurational entropy from molecular simulations via an expansion approximation
,” J. Chem. Phys.
127
(2
), 024107
(2007
).94.
95.
M. M.
Lin
, “Timing correlations in proteins predict functional modules and dynamic allostery
,” J. Am. Chem. Soc.
138
(15
), 5036
–5043
(2016
).96.
O. F.
Lange
and H.
Grubmüller
, “Generalized correlation for biomolecular dynamics
,” Proteins
62
(4
), 1053
–1061
(2006
).97.
A. R.
Atilgan
, P.
Akan
, and C.
Baysal
, “Small-world communication of residues and significance for protein dynamics
,” Biophys. J.
86
(1
), 85
–91
(2004
).98.
F.
Chung
, L.
Lu
, and V.
Vu
, “Spectra of random graphs with given expected degrees
,” Proc. Natl. Acad. Sci. U. S. A.
100
(11
), 6313
–6318
(2003
).99.
M. E.
Newman
and M.
Girvan
, “Finding and evaluating community structure in networks
,” Phys. Rev. E
69
(2 Pt 2
), 026113
(2004
).100.
M. E. J.
Newman
, “Modularity and community structure in networks
,” Proc. Natl. Acad. Sci. U. S. A.
103
(23
), 8577
–8582
(2006
).101.
A.
del Sol
, H.
Fujihashi
, D.
Amoros
, and R.
Nussinov
, “Residue centrality, functionally important residues, and active site shape: Analysis of enzyme and non-enzyme families
,” Protein Sci.
15
(9
), 2120
–2128
(2006
).102.
O.
Sheik Amamuddy
, R.
Afriyie Boateng
, V.
Barozi
, D.
Wavinya Nyamai
, and Ö.
Tastan Bishop
, “Novel dynamic residue network analysis approaches to study allosteric modulation: SARS-CoV-2 Mpro and its evolutionary mutations as a case study
,” Comput. Struct. Biotechnol. J.
19
, 6431
–6455
(2021
).103.
L.
Metcalf
and W.
Casey
, “Graph theory
,” in Cybersecurity and Applied Mathematics
, edited by L.
Metcalf
and W.
Casey
(Syngress
, Boston
, 2016
), Chap. 5, pp. 67
–94
.104.
P. V.
Marsden
, “Network analysis
,” in Encyclopedia of Social Measurement
, edited by K.
Kempf-Leonard
(Elsevier
, New York
, 2005
), pp. 819
–825
.105.
R. W.
Floyd
, “Algorithm 97: Shortest path
,” Commun. ACM
5
, 345
(1962
).106.
D.
Foutch
, B.
Pham
, and T.
Shen
, “Protein conformational switch discerned via network centrality properties
,” Comput. Struct. Biotechnol. J.
19
, 3599
–3608
(2021
).107.
D.
Mistry
, R. P.
Wise
, and J. A.
Dickerson
, “DiffSLC: A graph centrality method to detect essential proteins of a protein-protein interaction network
,” PLoS One
12
(11
), e0187091
(2017
).108.
C. F. A.
Negre
, U. N.
Morzan
, H. P.
Hendrickson
, R.
Pal
, G. P.
Lisi
, J. P.
Loria
, I.
Rivalta
, J.
Ho
, and V. S.
Batista
, “Eigenvector centrality for characterization of protein allosteric pathways
,” Proc. Natl. Acad. Sci. U. S. A.
115
(52
), E12201
–E12208
(2018
).109.
D. A.
Walsh
, J. P.
Perkins
, and E. G.
Krebs
, “An adenosine 3',5'-monophosphate-dependant protein kinase from rabbit skeletal muscle
,” J. Biol. Chem.
243
(13
), 3763
–3765
(1968
).110.
S. S.
Taylor
, R.
Ilouz
, P.
Zhang
, and A. P.
Kornev
, “Assembly of allosteric macromolecular switches: Lessons from PKA
,” Nat. Rev. Mol. Cell Biol.
13
(10
), 646
–658
(2012
).111.
K. M.
Boeshans
, K. A.
Resing
, J. B.
Hunt
, N. G.
Ahn
, and J. B.
Shabb
, “Structural characterization of the membrane-associated regulatory subunit of type I cAMP-dependent protein kinase by mass spectrometry: Identification of Ser81 as the in vivo phosphorylation site of RIalpha
,” Protein Sci.
8
(7
), 1515
–1522
(1999
).112.
J. B.
Shabb
, “Physiological substrates of cAMP-dependent protein kinase
,” Chem. Rev.
101
(8
), 2381
–2411
(2001
).113.
L. W.
Slice
and S. S.
Taylor
, “Expression of the catalytic subunit of cAMP-dependent protein kinase in Escherichia coli
,” J. Biol. Chem.
264
(35
), 20940
–20946
(1989
).114.
D. R.
Knighton
, J. H.
Zheng
, L. F.
Ten Eyck
, V. A.
Ashford
, N. H.
Xuong
, S. S.
Taylor
, and J. M.
Sowadski
, “Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase
,” Science
253
(5018
), 407
–414
(1991
).115.
D. R.
Knighton
, J. H.
Zheng
, L. F.
Ten Eyck
, N. H.
Xuong
, S. S.
Taylor
, and J. M.
Sowadski
, “Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase
,” Science
253
(5018
), 414
–420
(1991
).116.
R. T.
Aimes
, W.
Hemmer
, and S. S.
Taylor
, “Serine-53 at the tip of the glycine-rich loop of cAMP-dependent protein kinase: Role in catalysis, P-site specificity, and interaction with inhibitors
,” Biochemistry
39
(28
), 8325
–8332
(2000
).117.
G. H.
Iyer
, S.
Garrod
, V. L.
Woods
, Jr., and S. S.
Taylor
, “Catalytic independent functions of a protein kinase as revealed by a kinase-dead mutant: Study of the Lys72His mutant of cAMP-dependent kinase
,” J. Mol. Biol.
351
(5
), 1110
–1122
(2005
).118.
H. S.
Meharena
, X.
Fan
, L. G.
Ahuja
, M. M.
Keshwani
, C. L.
McClendon
, A. M.
Chen
, J. A.
Adams
, and S. S.
Taylor
, “Decoding the interactions regulating the active state mechanics of eukaryotic protein kinases
,” PLoS Biol.
14
(11
), e2000127
(2016
).119.
A. C.
Bastidas
, M. S.
Deal
, J. M.
Steichen
, Y.
Guo
, J.
Wu
, and S. S.
Taylor
, “Phosphoryl transfer by protein kinase A is captured in a crystal lattice
,” J. Am. Chem. Soc.
135
(12
), 4788
–4798
(2013
).120.
I. V.
Khavrutskii
, B.
Grant
, S. S.
Taylor
, and J. A.
McCammon
, “A transition path ensemble study reveals a linchpin role for Mg2+ during rate-limiting ADP release from protein kinase A
,” Biochemistry
48
(48
), 11532
–11545
(2009
).121.
Z. Q.
Bao
, D. M.
Jacobsen
, and M. A.
Young
, “Briefly bound to activate: Transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis
,” Structure
19
(5
), 675
–690
(2011
).122.
J. M.
Steichen
, G. H.
Iyer
, S.
Li
, S. A.
Saldanha
, M. S.
Deal
, V. L.
Woods
, Jr., and S. S.
Taylor
, “Global consequences of activation loop phosphorylation on protein kinase A
,” J. Biol. Chem.
285
(6
), 3825
–3832
(2010
).123.
A. C.
Bastidas
, J.
Wu
, and S. S.
Taylor
, “Molecular features of product release for the PKA catalytic cycle
,” Biochemistry
54
(1
), 2
–10
(2015
).124.
G.
Veglia
and A.
Cembran
, “Role of conformational entropy in the activity and regulation of the catalytic subunit of protein kinase A
,” FEBS J.
280
(22
), 5608
–5615
(2013
).125.
L. R.
Masterson
, A.
Mascioni
, N. J.
Traaseth
, S. S.
Taylor
, and G.
Veglia
, “Allosteric cooperativity in protein kinase A
,” Proc. Natl. Acad. Sci. U. S. A.
105
(2
), 506
–511
(2008
).126.
S. S.
Taylor
, J.
Yang
, J.
Wu
, N. M.
Haste
, E.
Radzio-Andzelm
, and G.
Anand
, “PKA: A portrait of protein kinase dynamics
,” Biochim. Biophys. Acta
1697
(1–2
), 259
–269
(2004
).127.
D. A.
Johnson
, P.
Akamine
, E.
Radzio-Andzelm
, M.
Madhusudan
, and S. S.
Taylor
, “Dynamics of cAMP-dependent protein kinase
,” Chem. Rev.
101
(8
), 2243
–2270
(2001
).128.
J. A.
Adams
, “Kinetic and catalytic mechanisms of protein kinases
,” Chem. Rev.
101
(8
), 2271
–2290
(2001
).129.
A. P.
Kornev
, S. S.
Taylor
, and L. F.
Ten Eyck
, “A helix scaffold for the assembly of active protein kinases
,” Proc. Natl. Acad. Sci. U. S. A.
105
(38
), 14377
(2008
).130.
A. P.
Kornev
, N. M.
Haste
, S. S.
Taylor
, and L. F.
Ten Eyck
, “Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism
,” Proc. Natl. Acad. Sci. U. S. A.
103
(47
), 17783
(2006
).131.
J.
Hu
, L. G.
Ahuja
, H. S.
Meharena
, N.
Kannan
, A. P.
Kornev
, S. S.
Taylor
, and A. S.
Shaw
, “Kinase regulation by hydrophobic spine assembly in cancer
,” Mol. Cell. Biol.
35
(1
), 264
–276
(2015
).132.
K.
Henzler-Wildman
and D.
Kern
, “Dynamic personalities of proteins
,” Nature
450
(7172
), 964
–972
(2007
).133.
G. P.
Miller
and S. J.
Benkovic
, “Deletion of a highly motional residue affects formation of the Michaelis complex for Escherichia coli dihydrofolate reductase
,” Biochemistry
37
(18
), 6327
–6335
(1998
).134.
E.
Neria
and M.
Kuplus
, “Molecular dynamics of an enzyme reaction: Proton transfer in TIM
,” Chem. Phys. Lett.
267
(1
), 23
–30
(1997
).135.
N.
Chopra
, T. E.
Wales
, R. E.
Joseph
, S. E.
Boyken
, J. R.
Engen
, R. L.
Jernigan
, and A. H.
Andreotti
, “Dynamic allostery mediated by a conserved tryptophan in the tec family kinases
,” PLoS Comput. Biol.
12
(3
), e1004826
(2016
).136.
A.
Ostermann
, R.
Waschipky
, F. G.
Parak
, and G. U.
Nienhaus
, “Ligand binding and conformational motions in myoglobin
,” Nature
404
(6774
), 205
–208
(2000
).137.
Q.
Zhao
, “Dynamic model for enzyme action
,” Protein Pept. Lett.
18
(1
), 92
–99
(2011
).138.
B.
Lu
, C. F.
Wong
, and J. A.
McCammon
, “Release of ADP from the catalytic subunit of protein kinase A: A molecular dynamics simulation study
,” Protein Sci.
14
(1
), 159
–168
(2005
).139.
X.
Cheng
, C.
Phelps
, and S. S.
Taylor
, “Differential binding of cAMP-dependent protein kinase regulatory subunit isoforms Iα and IIβ to the catalytic subunit
,” J. Biol. Chem.
276
(6
), 4102
–4108
(2001
).140.
M. J.
Moore
, J. R.
Kanter
, K. C.
Jones
, and S. S.
Taylor
, “Phosphorylation of the catalytic subunit of protein kinase A. Autophosphorylation versus phosphorylation by phosphoinositide-dependent kinase-1
,” J. Biol. Chem.
277
(49
), 47878
–47884
(2002
).141.
J.
Yang
, L. F.
Ten Eyck
, N.-H.
Xuong
, and S. S.
Taylor
, “Crystal structure of a cAMP-dependent protein kinase mutant at 1.26A: New insights into the catalytic mechanism
,” J. Mol. Biol.
336
(2
), 473
–487
(2004
).© 2023 Author(s). Published under an exclusive license by AIP Publishing.
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