Protein-Ligand Interactions and Drug Design (Methods in Molecular Biology, 2266)

334 Pages·2021·10.19 MB·English

by  Flavio Ballante (editor)

Methods in
Molecular Biology 2266
Flavio Ballante Editor
Protein-Ligand
Interactions
and Drug Design
M M B
ETHODS IN OLECULAR IO LO GY
SeriesEditor
JohnM.Walker
School of Lifeand MedicalSciences
University ofHertfordshire
Hatfield, Hertfordshire, UK
Forfurther volumes:
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Protein-Ligand Interactions and
Drug Design
Edited by
Flavio Ballante
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
Editor
FlavioBallante
DepartmentofCellandMolecularBiology
UppsalaUniversity
Uppsala,Sweden
ISSN1064-3745 ISSN1940-6029 (electronic)
MethodsinMolecularBiology
ISBN978-1-0716-1208-8 ISBN978-1-0716-1209-5 (eBook)
https://doi.org/10.1007/978-1-0716-1209-5
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Preface
Drug discovery has profoundly changed in the past few decades. The ceaseless increase in
structuraldataandthedevelopmentofcomputer technologyallowustosimulatecomplex
biological systems and study protein–ligand interactions, at the atomic level, with a speed
unthinkableuntilafewyearsago.Also,sincetheongoingexplosioninthesizeofaccessible
chemicalspaceandcommerciallibrariesofcompounds,itisnowfeasibletosearchfor new
ligandsindatabasesofseveralhundredmillionmolecules,withinafewweeks.Itissafetosay
thatcomputer-aideddrugdesignisanessentialtooltoacceleratethedrugdiscoveryprocess
and reduce failures and costs by avoiding the mere trial-and-error search practice. Protein-
Ligand Interactions and Drug Design collects modern and established computer-based
methods aimed at addressing the drug discovery challenge from disparate perspectives by
exploitinginformationonligand–proteinrecognition.Duetotheinfluenceoftheexplored
chemical space on finding new protein–ligand interaction patterns, techniques aimed to
explore or design novel ligand chemotypes are also enclosed in this volume. Chapters are
groupedaccordingtotheirunderlyingaimintothreemajorsectionswhichareorganizedin
a logical order. In Section I: Chemical Space, methods that allow for the exploration of
specific areas of chemical space and the designing of virtual libraries are presented.
SectionII:HitIdentificationandHit-to-LeadOptimizationincludesaplethoraofdifferent
approaches,basedonprotein–ligandinteractions,forliganddiscoveryanddesign.Finally,in
Section III: Drug Repurposing, Polypharmacology, and Target Identification are
reported methods aimed at drug repositioning or exploiting an ensemble of protein struc-
turesfortheidentificationofligandswithtailoredpolypharmacologicalprofilesornovelpro-
teintargets.
The main goal of this volume is to provide detailed practical procedures of solid
computer-aideddrugdesignmethodologiesemployedtorationalizeandoptimizeprotein–-
ligandinteractions.Thisbookisaimednotonlyatscientistswithexperienceindrugdesign
butalsoatthosewhoarenewtothefield.
Uppsala,Sweden FlavioBallante
v
Acknowledgments
Iwouldliketothankalltheauthorsthatcontributedtotherealizationofthisvolume,aswell
as the Series Editor Prof. John Walker, Mr. David C. Casey, Ms. Anna Rakovsky, and the
teamatHumanaPressfortheirpreciousguidanceduringtherealizationofthisbook.Many
thanksalsotoallthegreatscientistsandcollaboratorsIhavemetsofarwhogreatlyinspired
andenrichedmyresearchjourney,inparticulartoProf.JensCarlsson(UppsalaUniversity),
Prof. Gilbert Kirsch (University of Lorraine), Prof. Garland R. Marshall (Washington
UniversityinSt.Louis),andDr.ChrisM.Ho(DrugDesignMethodologies,LLC).
This volume is dedicated to Prof. Garland R. Marshall on the occasion of his
81stbirthday.
vii
Contents
Preface ..................................................................... v
Acknowledgments............................................................. vii
Contributors................................................................. xi
AbouttheEditor ............................................................. xv
PART I CHEMICAL SPACE
1 InvestigationoftheClick-ChemicalSpaceforDrugDesignUsing
ZINClick .............................................................. 3
AlbertoMassarotti
2 MolecularScaffoldHoppingviaHolisticMolecularRepresentation........... 11
FrancescaGrisoniandGisbertSchneider
PART II HIT IDENTIFICATION AND HIT-TO-LEAD OPTIMIZATION
3 BiasedDockingforProtein–LigandPosePrediction......................... 39
JuanPabloArcon,Adria´nG.Turjanski,MarceloA.Martı´,
andStefanoForli
4 BindingModePredictionandVirtualScreeningApplications
byCovalentDocking.................................................... 73
AndreaScarpino,Gy¨orgyG.Ferenczy,andGy¨orgyM.Keseru˝
5 Ligand–ReceptorInteractionsandDrugDesign............................ 89
AggelikiSyriopoulou,IoannisMarkopoulos,AndreasG.Tzakos,
andThomasMavromoustakos
6 SimulationofLigandTransportinReceptorsUsingCaverDock .............. 105
JanaHozzova´,OndrˇejVa´vra,DavidBedna´rˇ,andJirˇı´ Filipovicˇ
7 NegativeImage-BasedScreening:RigidDockingUsingCavity
Information............................................................ 125
PekkaA.Postila,SamiT.Kurkinen,andOlliT.Pentika€inen
8 NegativeImage-BasedRescoring:UsingCavityInformation
toImproveDockingScreening ........................................... 141
OlliT.Pentika€inenandPekkaA.Postila
9 Fragment-BasedDrugDesignofSelectiveHDAC6Inhibitors................ 155
DusanRuzic,NemanjaDjokovic,andKatarinaNikolic
10 AProtocoltoUseComparativeBindingEnergyAnalysis
toEstimateDrug-TargetResidenceTime.................................. 171
GauravK.Ganotra,ArianeNunes-Alves,
andRebeccaC.Wade
11 DynamicDockingUsingMulticanonicalMolecularDynamics:
SimulatingComplexFormationattheAtomisticLevel ...................... 187
Gert-JanBekkerandNarutoshiKamiya
ix
x Contents
12 FreeEnergyCalculationsforProtein–LigandBindingPrediction............. 203
WillemJespers,JohanÅqvist,andHugoGutie´rrez-de-Tera´n
13 ExploitingWaterDynamicsforPharmacophoreScreening................... 227
DavidSchaller,SzymonPach,MarcelBermudez,andGerhardWolber
14 MarkovStateModelstoElucidateLigandBindingMechanism............... 239
YunhuiGeandVincentA.Voelz
PART III DRUG REPURPOSING, POLYPHARMACOLOGY, AND TARGET
IDENTIFICATION
15 FromHomologyModelingtotheHitIdentificationandDrug
Repurposing:AStructure-BasedApproachintheDiscovery
ofNovelPotentialAnti-ObesityCompounds............................... 263
Giosue` Costa,AnnaArtese,FrancescoOrtuso,andStefanoAlcaro
16 MultipleTargetDrugDesignUsingLigBuilder3 .......................... 279
XiaoyuQing,ShiweiWang,YaxiaYuan,JianfengPei,
andLuhuaLai
17 Bionoi:AVoronoiDiagram-BasedRepresentationofLigand-Binding
SitesinProteinsforMachineLearningApplications......................... 299
JosephFeinstein,WentaoShi,J.Ramanujam,andMichalBrylinski
18 MDock:ASuiteforMolecularInverseDockingandTargetPrediction........ 313
ZhiweiMaandXiaoqinZou
Index ...................................................................... 323
Contributors
STEFANO ALCARO • DipartimentodiScienzedellaSalute,Universit`adegliStudi“Magna
Græcia”diCatanzaro,Campus“S.Venuta”,Catanzaro,Italy;Net4ScienceAcademic
Spin-Off,Universit`adegliStudi“MagnaGræcia”diCatanzaro,Campus“S.Venuta”,
Catanzaro,Italy
JOHANÅQVIST • DepartmentofCellandMolecularBiology,BiomedicalCenter,
UppsalaUniversity,Uppsala,Sweden
JUANPABLO ARCON • DepartamentodeQuı´micaBiol(cid:2)ogicaeIQUIBICEN-UBA/
CONICET,FacultaddeCienciasExactasyNaturales,UniversidaddeBuenosAires,
CiudadUniversitaria,BuenosAires,Argentina;InstituteforResearchinBiomedicine
(IRBBarcelona),TheBarcelonaInstituteofScienceandTechnology,Barcelona,Spain
ANNAARTESE • DipartimentodiScienzedellaSalute,Universit`adegliStudi“Magna
Græcia”diCatanzaro,Campus“S.Venuta”,Catanzaro,Italy;Net4ScienceAcademic
Spin-Off,Universit`adegliStudi“MagnaGræcia”diCatanzaro,Campus“S.Venuta”,
Catanzaro,Italy
DAVIDBEDNA´Rˇ • DepartmentofExperimentalBiologyandRECETOX,FacultyofScience,
MasarykUniversity,Brno,CzechRepublic
GERT-JANBEKKER • InstituteforProteinResearch,OsakaUniversity,Suita,Osaka,Japan
MARCELBERMUDEZ • PharmaceuticalandMedicinalChemistry,FreieUniversita€tBerlin,
Berlin,Germany
MICHAL BRYLINSKI • Center forComputationandTechnology,LouisianaStateUniversity,
BatonRouge,LA,USA;DepartmentofBiologicalSciences,LouisianaStateUniversity,
BatonRouge,LA,USA
GIOSUE` COSTA • DipartimentodiScienzedellaSalute,Universit`adegliStudi“Magna
Græcia”diCatanzaro,Campus“S.Venuta”,Catanzaro,Italy;Net4ScienceAcademic
Spin-Off,Universit`adegliStudi“MagnaGræcia”diCatanzaro,Campus“S.Venuta”,
Catanzaro,Italy
NEMANJA DJOKOVIC • DepartmentofPharmaceuticalChemistry,FacultyofPharmacy,
UniversityofBelgrade,Belgrade,Serbia
JOSEPH FEINSTEIN • Center forComputationandTechnology,LouisianaStateUniversity,
BatonRouge,LA,USA
GYO¨RGYG.FERENCZY • MedicinalChemistryResearchGroup,ResearchCentreforNatural
Sciences,Budapest,Hungary
JIRˇI´ FILIPOVICˇ • InstituteofComputerScience,MasarykUniversity,Brno,CzechRepublic
STEFANOFORLI • DepartmentofIntegrativeStructuralandComputationalBiology,Scripps
Research,LaJolla,CA,USA
GAURAVK.GANOTRA • MolecularandCellularModelingGroup,HeidelbergInstitutefor
TheoreticalStudies,Heidelberg,Germany
YUNHUIGE • DepartmentofChemistry,TempleUniversity,Philadelphia,PA,USA
FRANCESCAGRISONI • DepartmentofChemistryandAppliedBiosciences,RETHINK,ETH
Zurich,Zurich,Switzerland
HUGOGUTIE´RREZ-DE-TERA´N • DepartmentofCellandMolecularBiology,Biomedical
Center,UppsalaUniversity,Uppsala,Sweden
xi