Proteomics and Protein-Protein Interactions: Biology, Chemistry, Bioinformatics, and Drug Design (Protein Reviews)

325 Pages·2005·4.18 MB·English

by  Gabriel Waksman

Proteomics and Protein-Protein
Interactions
Biology, Chemistry, Bioinformatics,
and Drug Design
PROTEIN REVIEWS
EditorialBoard:
EDITOR-IN-CHIEF:M.ZOUHAIRATASSI,BaylorCollegeofMedicine,Houston,Texas
EDITORIALBOARD:LAWRENCEJ.BERLINER,UniversityofDenver,Denver,Colorado
ROWENJUI-YOACHANG,UniversityofTexas,Houston,Texas
HANSJO¨RNVALL,KarolinskaInstitutet,Stockholm,Sweden
GEORGEL.KENYON,UniversityofMichigan,AnnArbor,Michigan
BRIGITTEWITTMAN-LIEBOLD,WittmanInstituteofTechnologyand
Analysis,Tetlow,Germany
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Proteomics and Protein-
Protein Interactions
Biology, Chemistry, Bioinformatics,
and Drug Design
Protein Reviews Volume 3
Editedby
Gabriel Waksman
InstituteofStructuralMolecularBiology
BirkbeckandUniversityCollegeLondon
UnitedKingdom
LibraryofCongressCataloging-in-PublicationData
Proteomicsandprotein-proteininteractions:biology,chemistry,bioinformatics,anddrug
design/GabrielWaksman,editor.
p. cm.—(Proteinreviews)
Includesbibliographicalreferencesandindex.
ISBN0-387-24531-6
1.Protein-proteininteractions. 2.Proteomics. I.Waksman,Gabriel. II.Series.
QP551.5.P7652005
612(cid:1).01575—dc22 2005040224
ISBN-10:0-387-24531-6 e-ISBN0-387-24532-4 Printedonacid-freepaper.
ISBN-13:978-0387-24531-7
(cid:2)C 2005SpringerScience+BusinessMedia,Inc.
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Preface
GabrielWaksman
InstituteofStructuralMolecularBiology,BirkbeckandUniversityCollegeLondon,
MaletStreet,LondonWC1E7HX,UnitedKingdom
Addressforcorrespondence:
ProfessorGabrielWaksman
InstituteofStructuralMolecularBiology
BirkbeckandUniversityCollegeLondon
MaletStreet
LondonWC1E7H
UnitedKingdom
Email:[email protected]@ucl.ac.uk
Phone:[phone]
Fax:[phone]
URL:http://people.cryst.bbk.ac.uk/∼ubcg54a
Gabriel Waksman is Professor of Structural Molecular Biology at the Institute of
Structural Molecular Biology at UCL/Birkbeck, of which he is also the director.
BeforejoiningthefacultyofUCLandBirkbeck,hewastheRoyandDianaVagelos
Professor of Biochemistry and Molecular Biophysics at the Washington University
SchoolofMedicineinStLouis(USA).
Therapidlyevolvingfieldofproteinsciencehasnowcometorealizetheubiquity
andimportanceofprotein–proteininteractions.Ithadbeenknownforsometimethat
proteinsmayinteractwitheachothertoformfunctionalcomplexes,butitwasthought
tobethepropertyofonlyahandfulofkeyproteins.However,withtheadventofhigh-
throughputproteomicstomonitorprotein–proteininteractionsatanorganismlevel,
we can now safely state that protein–protein interactions are the norm and not the
exception. Thus, protein function must be understood in the larger context of the
variousbindingcomplexesthateachproteinmayformwithinteractingpartnersata
v
vi Preface
giventimeinthelifecycleofacell.Proteinsarenowseenasformingsophisticated
interactionnetworkssubjecttoremarkableregulation.Thestudyoftheseinteraction
networksandregulatorymechanism,whichIwouldliketoterm“systemsproteomics,”
isoneofthethrivingfieldsofproteomics.
The birds-eye view that systems proteomics offers should not, however, mask
thefactthatproteinsareeachcharacterizedbyauniquesetofphysicalandchemical
properties.Inotherwords,noproteinlooksandbehaveslikeanother.Thiscompli-
catesenormouslythedesignofhigh-throughputproteomicsmethods.Unlikegenes,
which,byandlarge,displaysimilarphysicochemicalbehaviorsandthuscanbeeasily
usedinahigh-throughputmode,proteinsarenoteasilyamenabletothesametreat-
ment.Itisthusimportanttoremindresearchersactiveintheproteomicsfieldofthe
fundamentalbasisofproteinchemistry.Thisbookattemptstobridgethetwoextreme
endsofproteinscience:ononeend,systemsproteomics,whichdescribes,atasystem
level,theintricateconnectionnetworkthatproteinsforminacell,andontheother
end, protein chemistry and biophysics, which describe the molecular properties of
individualproteinsandthestructuralandthermodynamicbasisoftheirinteractions
withinthenetwork.
Bridgingthetwoendsofthespectrumisbioinformaticsandcomputationalchem-
istry.Largedatasetscreatedbysystemsproteomicsneedtobeminedformeaningful
information,methodsneedtobedesignedandimplementedtoimproveexperimental
designs,extractsignalovernoise,andrejectartifacts,andpredictivemethodsneedto
beworkedoutandputtothetest.Computationalchemistryfacessimilarchallenges.
The prediction of binding thermodynamics of protein–protein interaction is still in
itsinfancy.Proteinsarelargeobjects,andsimplifyingassumptionsandshortcutsstill
need to be applied to make simulations manageable, and this despite exponential
progressincomputertechnology.
Finally,thestudyofproteinsimpactsdirectlyonhumanhealth.Itisanobvious
statement to say that, for decades, enzymes, receptors, and key regulator proteins
havebeentargetedfordrugdiscovery.However,arecentandexcitingdevelopment
is the exploitation of our knowledge of protein–protein interaction for the design
ofnewpharmaceuticals.Thispresentsparticularchallengesbecauseprotein–protein
interfaces are generally shallow and interactions are weak. However, progress is
clearlybeingmadeandthebookseekstoprovideexamplesofsuccessesinthisarea.
Iwouldliketothankallcontributorsfortheirparticipationtothisbook,which,
I believe, is timely and provides a good overview of the field. It is their hard work
that has made this book what it is, a fascinating foray into the complex world of
protein science. Proteomics and Protein-Protein Interactions: Biology. Chemistry.
Bioinformatics.AndDrugDesign.
GabrielWaksman
Contents
Preface v
GabrielWaksman
1. Introduction 01
GabrielWaksmanandClaireSansom
2. YeastTwo-HybridProtein–ProteinInteractionNetworks 19
DanielAuerbachandIgorStagljar
3. TheUseofMassSpectrometryinStudyingProtein–ProteinInteraction 33
YiWang,ParvinYazdi,andJunQin
4. MolecularRecognitionintheImmuneSystem 49
EricJ.SundbergandRoyA.Mariuzza
5. ComputationalMethodsforPredictingProtein–ProteinInteractions 89
A.Walker-TaylorandD.T.Jones
6. Protein–ProteinDockingMethods 115
GarlandR.MarshallandIlyaA.Vakser
7. ThermochemistryofBinaryandTernaryProteinInteractionsMeasured
byTitrationCalorimetry:ComplexFormationofCD4,HIVgp120,and
Anti-gp120 147
MichaelL.DoyleandPrestonHensley
8. Protein–Protein Recognition in Phosphotyrosine-Mediated Intracellular
Signaling 165
JohnE.Ladbury
9. CompetitiveBindingofProline-RichSequencesbySH3,WW,andOther
FunctionallyRelatedProteinDomains 185
MariusSudolandMarkT.Bedford
vii
viii Contents
10. TheStructureandMolecularInteractionsoftheBromodomain 203
KelleyS.YanandMing-MingZhou
11. SMARTDrugDesign:NovelPhosphopeptideandATPMimetic-Based
SmallMoleculeInhibitorsoftheOncogenicProteinKinasepp60src(Src) 219
T.K.Sawyer,R.S.Bohacek,W.C.Shakespeare,C.A.Metcalf,III,
Y.Wang,R.Sundaramoorthi,T.Keenan,S.Narula,andD.C.Dalgarno
12. DisruptingProtein–ProteinInteraction:TherapeuticToolsAgainstBrain
Damage 255
MichelleAartsandMichaelTymianski
13. AThermodynamicGuidetoAffinityOptimizationofDrugCandidates 291
ErnestoFreire
Index 309
1
Introduction: Proteomics and
Protein–Protein Interactions:
Biology, Chemistry,
Bioinformatics, and Drug
Design
Gabriel Waksman and Clare Sansom
ABSTRACT
In this chapter, a general introduction to the book is provided. We explain the organization
of the book and how the chapters are interconnected to each other. We also provide some
illustrationsandhighlightsthatwillcomplementthevariouschapters.
1. INTRODUCTION
The formidable advances in protein sciences in recent years have highlighted
theimportanceofprotein–proteininteractionsinbiology.Beforetheproteomicsrev-
olution,weknewthatproteinswerecapableofinteractingwitheachotherandthat
proteinfunctionwasregulatedbyinteractingpartners.However,theextentanddegree
oftheprotein–proteininteractionnetworkwasnotrealized.Itisnowbelievedthatnot
(cid:1)
GABRIELWAKSMANANDCLARESANSOM InstituteofStructuralMolecularBiology,Birkbeck
andUniversityCollegeLondon,MaletStreet,LondonWC1E7HX,UK.
ProteomicsandProtein–ProteinInteractions:Biology,Chemistry,Bioinformatics,andDrugDesign,
editedbyWaksman.Springer,NewYork,2005.
1