Amber 10

304 Pages·2008·0.99 MB·English

Amber 10
Users’ Manual
Principalcontributorstothecurrentcodes:
DavidA.Case(TheScrippsResearchInstitute) KimF.Wong(UniversityofUtah)
TomDarden(NIEHS) FrancescoPaesani(UniversityofUtah)
ThomasE.CheathamIII(Utah) JiriVanicek(EPL-Lausanne)
CarlosSimmerling(StonyBrook) XiongwuWu(NIH)
JunmeiWang(UTSouthwesternMedicalCenter) ScottR.Brozell(TSRI)
RobertE.Duke(NIEHSandUNC-ChapelHill) ThomasSteinbrecher(TSRI)
RayLuo(UCIrvine) HolgerGohlke(Kiel)
MikeCrowley(NREL) LijiangYang(UCIrvine)
RossWalker(SDSC) ChunhuTan(UCIrvine)
WeiZhang(TSRI) JohnMongan(UCSanDiego)
KennethM.Merz(Florida) ViktorHornak(StonyBrook)
BingWang(Florida) GuangleiCui(StonyBrook)
SethHayik(Florida) DavidH.Mathews(Rochester)
AdrianRoitberg(Florida) MatthewG.Seetin(Rochester)
GustavoSeabra(Florida) CelesteSagui(NorthCarolinaState)
IstvánKolossváry(BudapestandD.E.Shaw) VolodymyrBabin(NorthCarolinaState)
PeterA.Kollman(UCSanFrancisco)
Additionalkeycontributorstoearlierversions:
DavidA.Pearlman(UCSanFrancisco) VickieTsui(TSRI)
RobertV.Stanton(UCSanFrancisco) ChristianSchafmeister(Pitt)
JedPitera(UCSanFrancisco) WilsonS.Ross(UCSanFrancisco)
IrinaMassova(UCSanFrancisco) RandallRadmer(UCSanFrancisco)
AilanCheng(PennState) GeorgeL.Seibel(UCSanFrancisco)
JamesJ.Vincent(PennState) JamesW.Caldwell(UCSanFrancisco)
PaulBeroza(Telik) U.ChandraSingh(UCSanFrancisco)
PaulWeiner(UCSanFrancisco)
Additionalkeypeopleinvolvedinforcefielddevelopment:
PiotrCieplak(BurnhamInstitute) AlexeyOnufriev(VirginiaTech.)
YongDuan(U.C.Davis) ChristopherBayly(Merck-Frost)
RobWoods(Georgia) WendyCornell(UCSanFrancisco)
KarlKirschner(Georgia) ScottWeiner(UCSanFrancisco)
SarahM.Tschampel(Georgia) AustinYongye(Georgia)
MatthewTessier(Georgia)
1
Acknowledgments
ResearchsupportfromDARPA,NIHandNSFforPeterKollmanisgratefullyacknowledged,
asissupportfromNIH,NSF,ONRandDOEforDavidCase. UseofthefacilitiesoftheUCSF
Computer Graphics Laboratory (Thomas Ferrin, PI) is appreciated. The pseudocontact shift
codewasprovidedbyIvanoBertinioftheUniversityofFlorence. WethankChrisBaylyand
Merck-Frosst, Canada for permission to include charge increments for the AM1-BCC charge
scheme.Manypeoplehelpedaddfeaturestovariouscodes;thesecontributionsaredescribedin
thedocumentationfortheindividualprograms;seealsohttp://amber.scripps.edu/contributors.html.
RecommendedCitations:
WhencitingAmberVersion10intheliterature,thefollowingcitationshouldbeused:
D.A.Case,T.A.Darden,T.E.Cheatham,III,C.L.Simmerling,J.Wang,R.E.Duke,R.Luo,
M.Crowley,R.C.Walker,W.Zhang,K.M.Merz,B.Wang,S.Hayik,A.Roitberg,G.Seabra,I.
Kolossváry,K.F.Wong,F.Paesani,J.Vanicek,X.Wu,S.R.Brozell,T.Steinbrecher,H.Gohlke,
L.Yang,C.Tan,J.Mongan,V.Hornak,G.Cui,D.H.Mathews,M.G.Seetin,C.Sagui,V.Babin,
andP.A.Kollman(2008),AMBER10,UniversityofCalifornia,SanFrancisco.
Thehistoryofthecodesandabasicdescriptionofthemethodscanbefoundintwopapers:
• D.A. Pearlman, D.A. Case, J.W. Caldwell, W.S. Ross, T.E. Cheatham, III, S. DeBolt,
D.Ferguson,G.Seibel,andP.Kollman. AMBER,apackageofcomputerprogramsfor
applyingmolecularmechanics,normalmodeanalysis,moleculardynamicsandfreeen-
ergycalculationstosimulatethestructuralandenergeticpropertiesofmolecules. Comp.
Phys. Commun. 91,1-41(1995).
• D.A.Case,T.Cheatham,T.Darden,H.Gohlke,R.Luo,K.M.Merz,Jr.,A.Onufriev,C.
Simmerling,B.WangandR.Woods. TheAmberbiomolecularsimulationprograms. J.
Computat. Chem. 26,1668-1688(2005).
PeterKollmandiedunexpectedlyinMay,2001. WededicateAmbertohismemory.
CoverIllustration
ThecovershowsE.coliKASI(FabB)fattyacidsynthase(pdbcode1fj4),adrugtargetof
particularinterestforthedevelopmentofnovelantibiotics.Overlayingtheenzymethechemical
formula of a naturally occurring inhibitor, thiolactomycin, is drawn with six "computational
alchemy"ligandtransformationsrecentlystudiedbyfreeenergycalculations.[1,2]Thepicture
waspreparedbyThomasSteinbrecherusingVMD,povray3.6andChemDraw.
2
Contents
Contents 3
1. Introduction 9
1.1. Whattoreadnext . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.2. InformationflowinAmber . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.2.1. Preparatoryprograms . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.2.2. Simulationprograms . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.2.3. Analysisprograms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.3. InstallationofAmber10 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.3.1. Moreinformationonparallelmachinesorclusters . . . . . . . . . . . 14
1.3.2. InstallingNon-StandardFeatures . . . . . . . . . . . . . . . . . . . . 15
1.3.3. InstallingonMicrosoftWindows. . . . . . . . . . . . . . . . . . . . . 15
1.3.4. Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
1.3.5. MemoryRequirements . . . . . . . . . . . . . . . . . . . . . . . . . . 16
1.4. Basictutorials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2. Sanderbasics 19
2.1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2. Credits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.3. Fileusage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.4. Exampleinputfiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
2.5. Overviewoftheinformationintheinputfile . . . . . . . . . . . . . . . . . . . 23
2.6. Generalminimizationanddynamicsparameters . . . . . . . . . . . . . . . . . 23
2.6.1. Generalflagsdescribingthecalculation . . . . . . . . . . . . . . . . . 23
2.6.2. Natureandformatoftheinput . . . . . . . . . . . . . . . . . . . . . . 24
2.6.3. Natureandformatoftheoutput . . . . . . . . . . . . . . . . . . . . . 25
2.6.4. Frozenorrestrainedatoms . . . . . . . . . . . . . . . . . . . . . . . . 27
2.6.5. Energyminimization . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.6.6. Moleculardynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.6.7. Self-GuidedLangevindynamics . . . . . . . . . . . . . . . . . . . . . 28
2.6.8. Temperatureregulation . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.6.9. Pressureregulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
2.6.10. SHAKEbondlengthconstraints . . . . . . . . . . . . . . . . . . . . . 32
2.6.11. Watercap . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
2.6.12. NMRrefinementoptions . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.7. Potentialfunctionparameters . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.7.1. Genericparameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
2.7.2. ParticleMeshEwald . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
3
CONTENTS
2.7.3. UsingIPSforthecalculationofnonbondedinteractions . . . . . . . . 38
2.7.4. Extrapointoptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
2.7.5. Polarizablepotentials . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
2.7.6. DipolePrinting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
2.7.7. DetailedMPITimings . . . . . . . . . . . . . . . . . . . . . . . . . . 41
2.8. Varyingconditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
2.9. Fileredirectioncommands . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
2.10.Gettingdebugginginformation . . . . . . . . . . . . . . . . . . . . . . . . . . 46
3. Forcefieldmodifications 51
3.1. TheGeneralizedBorn/SurfaceAreaModel . . . . . . . . . . . . . . . . . . . 51
3.1.1. GB/SAinputparameters . . . . . . . . . . . . . . . . . . . . . . . . . 53
3.1.2. ALPB(AnalyticalLinearizedPoisson-Boltzmann) . . . . . . . . . . . 56
3.2. Poisson-Boltzmanncalculations . . . . . . . . . . . . . . . . . . . . . . . . . 57
3.2.1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
3.2.2. Usageandkeywords . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
3.2.3. Exampleinputs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
3.3. EmpiricalValenceBond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
3.3.1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
3.3.2. Generalusagedescription . . . . . . . . . . . . . . . . . . . . . . . . 70
3.3.3. Biasedsampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
3.3.4. Quantizationofnucleardegreesoffreedom . . . . . . . . . . . . . . . 75
3.3.5. DistributedGaussianEVB . . . . . . . . . . . . . . . . . . . . . . . . 76
3.3.6. EVBinputvariablesandinterdependencies . . . . . . . . . . . . . . . 78
3.4. UsingtheAMOEBAforcefield . . . . . . . . . . . . . . . . . . . . . . . . . 84
3.5. QM/MMcalculations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
3.5.1. ThehybridQM/MMpotential . . . . . . . . . . . . . . . . . . . . . . 87
3.5.2. TheQM/MMinterfaceandlinkatoms . . . . . . . . . . . . . . . . . . 88
3.5.3. GeneralizedBornimplicitsolvent . . . . . . . . . . . . . . . . . . . . 89
3.5.4. EwaldandPME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
3.5.5. HintsforrunningsuccessfulQM/MMcalculations . . . . . . . . . . . 90
3.5.6. GeneralQM/MM&qmmmNamelistVariables . . . . . . . . . . . . . 91
3.5.7. LinkAtomSpecificQM/MM&qmmmNamelistVariables . . . . . . . 97
4. Samplingandfreeenergies 99
4.1. Thermodynamicintegration. . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
4.1.1. Basicinputsforthermodynamicintegration . . . . . . . . . . . . . . . 100
4.1.2. SoftcorePotentialsinThermodynamicIntegration . . . . . . . . . . . 102
4.2. Umbrellasampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
4.3. TargetedMD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
4.4. SteeredMolecularDynamics(SMD)andtheJarzynskiRelationship . . . . . . 108
4.4.1. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
4.4.2. Implementationandusage . . . . . . . . . . . . . . . . . . . . . . . . 109
4.5. ReplicaExchangeMolecularDynamics(REMD) . . . . . . . . . . . . . . . . 110
4.5.1. ChangestoREMDinAmber10 . . . . . . . . . . . . . . . . . . . . . 111
4.5.2. RunningREMDsimulations . . . . . . . . . . . . . . . . . . . . . . . 112
4
CONTENTS
4.5.3. RestartingREMDsimulations . . . . . . . . . . . . . . . . . . . . . . 113
4.5.4. Contentoftheoutputfiles . . . . . . . . . . . . . . . . . . . . . . . . 113
4.5.5. Majorchangesfromsanderwhenusingreplicaexchange . . . . . . . . 114
4.5.6. Cautionswhenusingreplicaexchange . . . . . . . . . . . . . . . . . . 115
4.5.7. Replicaexchangeexample . . . . . . . . . . . . . . . . . . . . . . . . 115
4.5.8. Replicaexchangeusingahybridsolventmodel . . . . . . . . . . . . . 117
4.5.9. ChangestohybridREMDinAmber10 . . . . . . . . . . . . . . . . . 118
4.5.10. Cautionsforhybridsolventreplicaexchange . . . . . . . . . . . . . . 118
4.5.11. ReservoirREMD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
4.6. AdaptivelybiasedMD,steeredMD,andumbrellasamplingwithREMD . . . . 121
4.6.1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
4.6.2. ReactionCoordinates . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
4.6.3. SteeredMolecularDynamics . . . . . . . . . . . . . . . . . . . . . . . 125
4.6.4. Umbrellasampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
4.6.5. AdaptivelyBiasedMolecularDynamics . . . . . . . . . . . . . . . . . 127
4.7. Nudgedelasticbandcalculations . . . . . . . . . . . . . . . . . . . . . . . . . 130
4.7.1. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
4.7.2. PreparinginputfilesforNEB . . . . . . . . . . . . . . . . . . . . . . 132
4.7.3. InputVariables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
4.8. ConstantpHcalculations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
4.8.1. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
4.8.2. PreparingasystemforconstantpH . . . . . . . . . . . . . . . . . . . 134
4.8.3. RunningatconstantpH. . . . . . . . . . . . . . . . . . . . . . . . . . 135
4.8.4. AnalyzingconstantpHsimulations . . . . . . . . . . . . . . . . . . . 136
4.8.5. ExtendingconstantpHtoadditionaltitratablegroups . . . . . . . . . . 137
4.9. Low-MODe(LMOD)methods . . . . . . . . . . . . . . . . . . . . . . . . . . 139
4.9.1. LMODconformationalsearchingandflexibledocking . . . . . . . . . 139
4.9.2. LMODProcedure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
4.9.3. XMIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
4.9.4. LMOD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
4.9.5. TricksofthetradeofrunningLMODsearches . . . . . . . . . . . . . 145
5. Quantumdynamics 147
5.1. Path-IntegralMolecularDynamics . . . . . . . . . . . . . . . . . . . . . . . . 147
5.1.1. Generaltheory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
5.1.2. HowPIMDworksinAmber . . . . . . . . . . . . . . . . . . . . . . . 149
5.2. CentroidMolecularDynamics(CMD) . . . . . . . . . . . . . . . . . . . . . . 153
5.2.1. Implementationandinput/outputfiles . . . . . . . . . . . . . . . . . . 154
5.2.2. Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
5.3. RingPolymerMolecularDynamics(RPMD) . . . . . . . . . . . . . . . . . . 156
5.3.1. Inputparameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
5.3.2. Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
5.4. ReactiveDynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
5.4.1. Pathintegralquantumtransitionstatetheory. . . . . . . . . . . . . . . 156
5.4.2. QuantumInstanton . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
5.5. Isotopeeffects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
5
CONTENTS
5.5.1. Thermodynamicintegrationwithrespecttomass . . . . . . . . . . . . 160
5.5.2. AMBERimplementation . . . . . . . . . . . . . . . . . . . . . . . . . 162
5.5.3. Equilibriumisotopeeffects . . . . . . . . . . . . . . . . . . . . . . . . 162
5.5.4. Kineticisotopeeffects . . . . . . . . . . . . . . . . . . . . . . . . . . 163
5.5.5. EstimatingthekineticisotopeeffectusingEVB/LES-PIMD . . . . . . 164
6. NMRandX-rayrefinementusingSANDER 167
6.1. Distance,angleandtorsionalrestraints . . . . . . . . . . . . . . . . . . . . . . 168
6.1.1. Variablesinthe&rstnamelist: . . . . . . . . . . . . . . . . . . . . . . 168
6.2. NOESYvolumerestraints . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
6.3. Chemicalshiftrestraints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
6.4. Pseudocontactshiftrestraints . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
6.5. Directdipolarcouplingrestraints . . . . . . . . . . . . . . . . . . . . . . . . . 180
6.6. ResidualCSAorpseudo-CSArestraints . . . . . . . . . . . . . . . . . . . . . 182
6.7. PreparingrestraintfilesforSander . . . . . . . . . . . . . . . . . . . . . . . . 183
6.7.1. Preparingdistancerestraints: makeDIST_RST . . . . . . . . . . . . . 183
6.7.2. Preparingtorsionanglerestraints: makeANG_RST . . . . . . . . . . . 187
6.7.3. Chiralityrestraints: makeCHIR_RST . . . . . . . . . . . . . . . . . . 189
6.7.4. Directdipolarcouplingrestraints: makeDIP_RST . . . . . . . . . . . . 189
6.8. GettingsummariesofNMRviolations . . . . . . . . . . . . . . . . . . . . . . 190
6.9. Time-averagedrestraints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
6.10.MultiplecopiesrefinementusingLES . . . . . . . . . . . . . . . . . . . . . . 192
6.11.Somesampleinputfiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
6.11.1. 1. SimulatedannealingNMRrefinement . . . . . . . . . . . . . . . . 192
6.11.2. PartoftheRST.ffilereferredtoabove . . . . . . . . . . . . . . . . . 193
6.11.3. 3. SampleNOESYintensityinputfile . . . . . . . . . . . . . . . . . . 195
6.11.4. Residualdipolarrestraints,preparedbymakeDIP_RST: . . . . . . . . 195
6.11.5. Amorecomplicatedconstraint . . . . . . . . . . . . . . . . . . . . . 196
6.12.X-rayCrystallographyRefinementusingSANDER . . . . . . . . . . . . . . . 197
7. PMEMD 199
7.1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
7.2. Functionality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
7.3. PMEMD-specificnamelistvariables . . . . . . . . . . . . . . . . . . . . . . . 201
7.4. Slightlychangedfunctionality . . . . . . . . . . . . . . . . . . . . . . . . . . 203
7.5. Parallelperformancetuningandhints . . . . . . . . . . . . . . . . . . . . . . 204
7.6. Installation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
7.7. Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
8. MM_PBSA 207
8.1. Generalinstructions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
8.2. Inputexplanations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
8.2.1. General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
8.2.2. EnergyDecompositionParameters . . . . . . . . . . . . . . . . . . . . 210
8.2.3. Poisson-BoltzmannParameters . . . . . . . . . . . . . . . . . . . . . 211
8.2.4. MolecularMechanicsParameters . . . . . . . . . . . . . . . . . . . . 213
6
CONTENTS
8.2.5. GeneralizedBornParameters . . . . . . . . . . . . . . . . . . . . . . 213
8.2.6. MolsurfParameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
8.2.7. NMODEParameters . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
8.2.8. ParametersforSnapshotGeneration . . . . . . . . . . . . . . . . . . . 213
8.2.9. ParametersforAlanineScanning . . . . . . . . . . . . . . . . . . . . 214
8.2.10. TrajectorySpecification . . . . . . . . . . . . . . . . . . . . . . . . . 215
8.3. Preparingtheinputfile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
8.4. AuxiliaryprogramsusedbyMM_PBSA . . . . . . . . . . . . . . . . . . . . . 222
8.5. APBSasanalternatePBsolverinSander . . . . . . . . . . . . . . . . . . . . 222
9. LES 225
9.1. PreparingtouseLESwithAMBER . . . . . . . . . . . . . . . . . . . . . . . 225
9.2. UsingtheADDLESprogram . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
9.3. MoreinformationontheADDLEScommandsandoptions . . . . . . . . . . . 229
9.4. Usingthenewtopology/coordinatefileswithSANDER . . . . . . . . . . . . . 230
9.5. UsingLESwiththeGeneralizedBornsolvationmodel . . . . . . . . . . . . . 231
9.6. Casestudies: ExamplesofapplicationofLES . . . . . . . . . . . . . . . . . . 232
9.6.1. Enhancedsamplingforindividualfunctionalgroups: Glucose . . . . . 232
9.6.2. Enhancedsamplingforasmallregion: ApplicationofLEStoanucleic
acidloop . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
9.6.3. Improvingconformationalsamplinginasmallpeptide . . . . . . . . . 234
10.Divcon 237
10.1.Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
10.2.GettingStarted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
10.2.1. StandardJobs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
10.2.2. DivideandConquerJobs . . . . . . . . . . . . . . . . . . . . . . . . . 238
10.3.Keywords . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
10.3.1. Hamiltonians . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
10.3.2. ConvergenceCriterion . . . . . . . . . . . . . . . . . . . . . . . . . . 239
10.3.3. RestrainedAtoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
10.3.4. Output . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
10.3.5. General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
10.3.6. Gradient. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
10.3.7. AtomicCharges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
10.3.8. Subsetting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
10.4.Solvation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
10.5.NuclearMagneticResonance(NMR) . . . . . . . . . . . . . . . . . . . . . . . 248
10.5.1. DefaultKeywords . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
10.6.CitationInformation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
11.Miscellaneous 251
11.1.ambpdb . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
11.2.protonate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
11.3.ambmask . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
11.4.pol_handgwh . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
7
CONTENTS
11.5.fantasian . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
11.6.elsize . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
A. NamelistInputSyntax 261
B. GROUPSpecification 263
C. EVBoutputfilespecifications 267
D. DistributedGaussianEVBformatspecifications 271
D.1. Cartesiancoordinaterepresentation. . . . . . . . . . . . . . . . . . . . . . . . 271
D.2. Internalcoordinaterepresentation . . . . . . . . . . . . . . . . . . . . . . . . 273
E. AMBERTrajectoryNetCDFFormat 275
E.1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
E.2. Programbehavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
E.3. NetCDFfileencoding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
E.4. Globalattributes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
E.5. Dimensions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
E.6. Variables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
E.6.1. Labelvariables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
E.6.2. Datavariables. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
E.7. Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
E.8. Extensionsandmodifications . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
E.9. Revisionhistory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Bibliography 283
Index 300
8
1. Introduction
Amberisthecollectivenameforasuiteofprogramsthatallowuserstocarryoutmolecular
dynamics simulations, particularly on biomolecules. None of the individual programs carries
thisname,butthevariouspartsworkreasonablywelltogether,andprovideapowerfulframe-
workformanycommoncalculations.[3,4]Thetermamberisalsosometimesusedtoreferto
the empirical force fields that are implemented here. [5,6] It should be recognized however,
thatthecodeandforcefieldareseparate: severalothercomputerpackageshaveimplemented
the amber force fields, and other force fields can be implemented with the amber programs.
Further, the force fields are in the public domain, whereas the codes are distributed under a
licenseagreement.
TheAmbersoftwaresuiteisnowdividedintotwoparts: AmberTools,acollectionoffreely
availableprogramsmostlyundertheGPLlicense,andAmber10,whichiscenteredaroundthe
sanderandpmemdsimulationprograms,andwhichcontinuestobelicensedasbefore,undera
morerestrictivelicense. Youneedtoinstallbothparts,startingwithAmberTools.
Amber10(2008)representsasignificantchangefromthemostrecentpreviousversion,Am-
ber9,whichwasreleasedinMarch,2006. Briefly,themajordifferencesinclude:
1. Newfreeenergytools,thatincorporatesoft-corepotentialsandremovetherequirement
tocreatedummyatomsundermostcircumstances. Calculationscanuseeither“single”
or“dual”topologymodels.
2. Muchbetterperformanceandparallelscalinginpmemd,whichhassupportforoff-center
charges (as in TIP4P or TIP5P) and for generalized Born calculations. A pmemd.amba
versionincludes(modest)parallelsupportfortheAmoebaproteinpotentials.
3. Anewsuiteofconformationalclusteringtoolsinptraj,andnewanalysistoolsforMM-
PBSA.
4. Betterintegrationof“low-mode”(LMOD)conformationalsearchtools,basedonfollow-
inglow-frequencynormalmodes.
5. Re-workedreplicaexchangedynamics(REMD),andnewmethodsforenhancedconfor-
mational searches using biased molecular dynamics. Non-Boltzmann reservoirs can be
involvedinexchanges.
6. Moreaccuratenonpolarimplicitsolventmodelsinpbsa.
7. Inclusion of NAB (Nucleic Acid Builder), which provides second derivatives of gener-
alized Born potentials, new methods of normal mode analysis, and a model-building
environmentforproteinsandnucleicacids.
8. New codes and data structures for manipulating molecules, including sleap, a replace-
mentandextensionfortleap.
9
1. Introduction
9. Updatedforcefieldsforcarbohydrates,lipids,nucleicacids,andionsandwater.
10. ExpandedQM/MMsupportwithsupportforPMEandGBbasedDFTBcalculations,as
wellasimprovedperformanceandparallelization.
1.1. What to read next
IfyouareinstallingthispackageseeSection1.3. NewusersshouldcontinuewiththisChap-
ter, and should consult the tutorial information in Section 1.4. There are also tips and exam-
plesontheAmberWebpagesathttp://ambermd.org. AlthoughAmbermayappeardauntingly
complexatfirst,ithasbecomeeasiertouseoverthepastfewyears,andoverallisreasonably
straightforwardonceyouunderstandthebasicarchitectureandoptionchoices.Inparticular,we
have worked hardon the tutorials to makethem accessible to new users. Hundreds of people
havelearnedtouseAmber;don’tbeeasilydiscouraged.
If you want to learn more about basic biochemical simulation techniques, there are a vari-
etyofgoodbookstoconsult, rangingfromintroductorydescriptions,[7,8]tostandardworks
on liquid state simulation methods, [9,10] to multi-author compilations that cover many im-
portantaspectsofbiomolecularmodelling.[11–13]Lookingfor"paradigm"papersthatreport
simulationssimilartoonesyoumaywanttoundertakeisalsogenerallyagoodidea.
1.2. Information flow in Amber
Understanding where to begin in Amber is primarily a problem of managing the flow of
information in this package–see Fig. 1.1. You first need to understand what information is
needed by the simulation programs (sander and pmemd). You need to know where it comes
from,andhowitgetsintotheformthattheenergyprogramsrequire. Thissectionismeantto
orientthenewuserandisnotasubstitutefortheindividualprogramdocumentation.
Informationthatallthesimulationprogramsneed:
1. Cartesiancoordinatesforeachatominthesystem. TheseusuallycomefromX-raycrys-
tallography,NMRspectroscopy,ormodel-building. TheyshouldbeinProteinDatabank
(PDB)orTripos"mol2"format. TheprogramLEaPprovidesaplatformforcarryingout
some of these modeling tasks, but users may wish to consider other programs as well,
includingtheNABprogrammingenvironmentinAmberTools.
2. "Topology": connectivity,atomnames,atomtypes,residuenames,andcharges. Thisin-
formationcomesfromthedatabase,whichisfoundintheamber10/dat/leap/prepdirec-
tory,andisdescribedinChapter2oftheAmberToolsmanual.Itcontainstopologyforthe
standardaminoacidsaswellasN-andC-terminalchargedaminoacids,DNA,RNA,and
common sugars. The database contains default internal coordinates for these monomer
units,butcoordinateinformationisusuallyobtainedfromPDBfiles. Topologyinforma-
tion for other molecules (not found in the standard database) is kept in user-generated
"residuefiles",whicharegenerallycreatedusingantechamber.
3. Forcefield: Parametersforallofthebonds,angles,dihedrals,andatomtypesinthesys-
tem.Thestandardparametersforseveralforcefieldsarefoundintheamber10/dat/leap/parm
10