Computer-Aided Drug Discovery

314 Pages·2016·7.74 MB·English

by  Wei Zhang (eds.)

Methods in Pharmacology
and Toxicology
Wei Zhang Editor
Computer-
Aided Drug
Discovery
M P
ETHODS IN H A R M A C O L O G Y
T
A N D OXICO LOGY
SeriesEditor
James Y. Kang
Departmentof Medicine
University ofLouisville School of Medicine
Prospect, Kentucky,USA
For further volumes:
http://www.springer.com/series/7653
.
Computer-Aided Drug
Discovery
Edited by
Wei Zhang
Chemistry Department, Southern Research Institute,
Birmingham, AL, USA
Editor
WeiZhang
ChemistryDepartment
SouthernResearchInstitute
Birmingham,AL,USA
ISSN1557-2153 ISSN1940-6053 (electronic)
MethodsinPharmacologyandToxicology
ISBN978-1-4939-3519-2 ISBN978-1-4939-3521-5 (eBook)
DOI10.1007/978-1-4939-3521-5
LibraryofCongressControlNumber:2016942864
#SpringerScience+BusinessMediaNewYork2016
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Preface
Computational technologies have been applied in drug discovery for decades and are
gaining increasingly in popularity, implementation, and appreciation due to the recent
advances in computational methodologies and the fast growth of low-cost high perfor-
mance computing techniques. Computer-aided drug discovery (CADD) has become a
crucial component of modern drug discovery programs and is widely utilized to identity
and optimize bioactive compounds for the development of new drugs. The intent of this
book is to provide a practical guide for solving drug discovery-related problems using
computationaltechniques.
CADDisadiversedisciplinewherevariousaspectsofappliedandbasicresearchmerge
andstimulateeachother.Computationalstrategiesthusneedtobefrequentlyadjustedfor
differentdrugdiscoverypurposes.Awidevarietyofcomputationalapproacheshavebeen
usedindifferentstagesofdrugdiscoveryanddevelopment,aswellasinclinicalstudies.Itis
not possible to comprehensively cover such a broad field in one volume. Therefore, this
bookfocusesonthemethodsthatarecommonlyusedintheearlystageofdrugdiscovery,
including computer simulation, structure prediction, conformational sampling, binding
sitemapping,dockingandscoring,insilicoscreening,andfragment-baseddrugdesign.In
addition to the state-of-the-art theoretical concept, this book also includes step-by-step,
readilyreproduciblecomputationalprotocolsaswellasexamplesofvariousCADDstrate-
gies.Thelimitationsandpotentialpitfallsofdifferentcomputationalmethodsarediscussed
byexperts,andtipsandadvicefor theirapplicationsaresuggested.
IthasbeenagreatprivilegetoworkwiththemanyexpertsintheCADDfield.Ivery
much appreciate the patience of the authors who carefully worked on their chapters and
tookintoconsiderationmycommentstomakethemapartofacoherentpicture.
I would like to dedicate this book to my dearly beloved grandfather, whose wisdom,
dedication,andpassionforlifehasalwaysbeenaninspirationfor me.
Birmingham,AL,USA WeiZhang
v

Contents
Preface.................................................................... v
Contributors............................................................... ix
MolecularDynamicsSimulationsandComputer-AidedDrugDiscovery.......... 1
RyanC.Godwin,RyanMelvin,andFreddieR.SalsburyJr.
AReviewofEvolutionaryAlgorithmsforComputingFunctional
ConformationsofProteinMolecules......................................... 31
AmardaShehu
IncorporatingReceptorFlexibilityintoStructure-BasedDrugDiscovery ......... 65
ChungF.Wong
UnderstandingWaterandItsManyRolesinBiologicalStructure:
WaystoExploitaResourceforDrugDiscovery ............................... 85
MostafaH.Ahmed,AlessioAmadasi,AlexanderS.Bayden,
DerekJ.Cashman,PietroCozzini,ChenxiaoDa,DeliangL.Chen,
MicaelaFornabaio,VishalN.Koparde,AndreaMozzarelli,
HardikI.Parikh,AurijitSarkar,J.NeelScarsdale,
FrancescaSpyrakis,J.AndrewSurface,AshutoshTripathi,
SaheemA.Zaidi,andGlenE.Kellogg
CAVITY:MappingtheDruggableBindingSite ............................... 111
WeilinZhang,YaxiaYuan,JianfengPei,andLuhuaLai
MethodsforDetectingProteinBindingInterfaces............................. 133
NuritHaspel
MDock:AnEnsembleDockingSuiteforMolecularDocking,Scoring
andInSilicoScreening..................................................... 153
ChengfeiYanandXiaoqinZou
PharmacophoreModeling:MethodsandApplications.......................... 167
DavidRyanKoes
ComputationalFragment-BasedDrugDesign................................. 189
ChunquanSheng,GuoqiangDong,andChenWang
ApplicationsoftheFragmentMolecularOrbitalMethod
toDrugResearch.......................................................... 217
MichaelP.Mazanetz,EwaChudyk,DmitriG.Fedorov,
andYuriAlexeev
RecentAdvancesintheOpenAccessCheminformatics Toolkits,
SoftwareTools,WorkflowEnvironments,andDatabases ....................... 257
PravinAmbure,RahulBalasahebAher,andKunalRoy
Index..................................................................... 297
vii

Contributors
RAHULBALASAHEBAHER (cid:1) DrugTheoreticsandCheminformaticsLaboratory,
DepartmentofPharmaceuticalTechnology,JadavpurUniversity,Kolkata,India
MOSTAFAH.AHMED (cid:1) DepartmentofMedicinalChemistry,SchoolofPharmacy,
VirginiaCommonwealthUniversity,Richmond,VA,USA;InstituteforStructural
Biology,DrugDiscoveryandDevelopment,VirginiaCommonwealthUniversity,
Richmond,VA,USA
YURIALEXEEV (cid:1) LeadershipComputingFacility,ArgonneNationalLaboratory,
Argonne,IL,USA
ALESSIO AMADASI (cid:1) DepartmentofFoodScience,UniversityofParma,Parma,Italy
PRAVINAMBURE (cid:1) DrugTheoreticsandCheminformatics Laboratory,Department
ofPharmaceuticalTechnology,JadavpurUniversity,Kolkata,India
ALEXANDERS.BAYDEN (cid:1) DepartmentofMedicinalChemistry,SchoolofPharmacy,
VirginiaCommonwealthUniversity,Richmond,VA,USA;InstituteforStructural
Biology,DrugDiscoveryandDevelopment,VirginiaCommonwealthUniversity,
Richmond,VA,USA;CMDBioscience,Inc.,NewHaven,CT,USA
DEREKJ.CASHMAN (cid:1) DepartmentofMedicinalChemistry,SchoolofPharmacy,
VirginiaCommonwealthUniversity,Richmond,VA,USA;InstituteforStructural
Biology,DrugDiscoveryandDevelopment,VirginiaCommonwealthUniversity,
Richmond,VA,USA;TennesseeTechnologicalUniversity,Cookeville,TN,USA
DELIANGL.CHEN (cid:1) DepartmentofMedicinalChemistry,SchoolofPharmacy,
VirginiaCommonwealthUniversity,Richmond,VA,USA;InstituteforStructural
Biology,DrugDiscoveryandDevelopment,VirginiaCommonwealthUniversity,
Richmond,VA,USA;CollegeofChemistryandChemicalEngineering,
GannanNormalUniversity,Ganzhou,Jiangxi,China
EWACHUDYK (cid:1) Evotec(UK)Ltd,Abingdon,Oxfordshire,UK
PIETROCOZZINI (cid:1) DepartmentofFoodScience,UniversityofParma,Parma, Italy
CHENXIAODA (cid:1) DepartmentofMedicinalChemistry,SchoolofPharmacy,
VirginiaCommonwealthUniversity,Richmond,VA,USA;InstituteforStructural
Biology,DrugDiscoveryandDevelopment,VirginiaCommonwealthUniversity,
Richmond,VA,USA
GUOQIANGDONG (cid:1) DepartmentofMedicinalChemistry,SchoolofPharmacy,
SecondMilitaryMedicalUniversity,Shanghai,People’sRepublicofChina
DMITRIG.FEDOROV (cid:1) NanomaterialsResearchInstitute,NationalInstitute
ofAdvancedIndustrialScienceandTechnology(AIST),Tsukuba,Japan
MICAELAFORNABAIO (cid:1) DepartmentofMedicinalChemistry,SchoolofPharmacy,
VirginiaCommonwealthUniversity,Richmond,VA,USA;InstituteforStructural
Biology,DrugDiscoveryandDevelopment,VirginiaCommonwealthUniversity,
Richmond,VA,USA
RYANC.GODWIN (cid:1) DepartmentofPhysics,WakeForestUniversity,Winston-Salem,NC,
USA
NURITHASPEL (cid:1) DepartmentofComputerScience,UniversityofMassachusettsBoston,
Boston,MA,USA
ix