CHARMM Tutorial

CHARMMTutorial:1.Gettingstarted2.FirststepsinCHARMM3.Manipulatingstructures4.Energyminimization5.Introductiontomoleculardynamics6.Moleculardynamicsofhomogeneoussystems7.Moleculardynamicsofsolvatedbiomolecules8.ComputingNMRproperties9.DistancerestraintsCHARMMTutorial1.Gettingstarted●1.1Introduction●1.2IntroductiontoUnixandsomeusefulutilities2.GettingstartedwithCHARMM●2.1Asimpleexample:Molecularmechanicsstudyofawaterdimer●2.2FromapdbcoordinatefiletotheCHARMMPSFandcoordinates●2.3UsingtheCHARMMbuilt-ingraphics3.ManipulatingandcomparingstructureswithCHARMM●3.1Manipulationofcoordinatesandinternalcoordinates,atomselection●3.2Comparisonofstructures●3.3Afinalsimpleexercise:Buildingofasmallpeptide4.Energyminimization●4.1Energycalculation●4.2Minimization●4.3Applications5.Introductiontomoleculardynamics(MD)andsimpleanalysis●5.1Preliminaryremarks●5.2SHAKE●5.3Afirstexample●5.4AnalysisofMDsimulationsinthegasphase●5.5Methodologicalcommentsandthingstotry●5.6Concludingexercise:gasphaseMDofN-acetyl-L-tryptophanemethylamide6.Moleculardynamicsofhomogeneoussystems(solvent)●6.1Periodicboundaryconditions(pbc)●6.2TheEwaldsummationmethod●6.3RunningaMDsimulation●6.4Analysiswiththefacility7.MDsimulationofsolvatedbiomolecules---analysisofresults●7.1Crambin●7.2Acomplexexercise:N-acetyl-L-tryptophanemethylamideinwater8.ComputingNMRpropertiesfromaMDsimulation9.DistancerestraintsCHARMMTutorial1.Gettingstarted1.1IntroductionScopeandgoalsofthecourse(Ãœbungen)Thecourseisintendedtofamiliarizeyouwithimportantconceptsofbiomolecularsimulation,energyminimizationandmoleculardynamics.ThisisdonebycarryingoutpracticalexamplesusingthesimulationprogramCHARMM.TheexercisesmayalsoserveasatutorialonhowtouseCHARMMthoughtheemphasisisontheprinciplesofthemethods,notthedetailsofthefunctionalityprovidedbytheprogram.Topicswereselectedaccordingtolessismore.Thus,thecoursedoesnotcovereveryaspectoforintroducesyoutoallcapabilitiesofCHARMM.Instead,theknowledgeyouhopefullywillhaveacquiredafterworkingthroughtheexamplesandexercisesshouldenableyoutouseCHARMM(oranotherbiomolecularsimulationpackage)intelligentlyinyourownwork,relyingonthe(terse)CHARMMdocumentationandthetestcasesthatcomewiththe(academic)distributionoftheprogramforfurtherhelp.TheaccompanyinglecturedealsinsomedetailwiththeprinciplesofbiomolecularNMR-spectroscopyandhowtechniquesofbiomolecularsimulationarerelatedtoandusedinstructuredeterminationofbiologicalmacromoleculesbyNMR.Inthecourse(�bungen),however,theemphasiswillbeonsimulationmethods.WhyCHARMM?Shortanswer:It'stheprogramIknowbest.Longanswer:ThereareanumberofreasonsthatmakeCHARMMverysuitableforuseinanintroductorycourse(whichisnottosaythatitisnotequallywellsuitedforresearchapplications!)Itisonesingleprogram,makingiteasiertouseandtolearnthanasuiteofsmallerprogramsthatoftenhavetobeforcedtointeractproperlywitheachother.Theuserinterfaceisfairlyuniform;inaddition,the(academic)versionofCHARMMisquiteup-to-datewithrespecttothelatestmethodologicaldevelopments.Obviously,foranumberofthingsprogramsexistwhichhandleaparticularproblemmuchmoreelegantlyorareeasiertouse.Inreallife,onemight,therefore,preferprogramXYZtoCHARMMinsuchinstances.However,inthecontextofthiscoursewedecidedthatitisbesttouseoneprogramforallapplicationsratherthanmakingyou(re)learnseveralprograms.TheproperreferenceforCHARMM(ChemistryatHARvardMolecularMechanics)is:B.R.Brooksetal.J.Comput.Chem.1983,4,187-217.Currently,anewversionofCHARMM,containingbug-fixesandnewfeatures,isreleasedappr.twiceayear.ToobtainCHARMM,onehastocontactProf.MartinKarplus(e-mail:[e-mail]@brel.u-strasbg.fr)Withrespecttocomputergraphics...Lessismorealsowasthereasonwhynointroductiontoahigh-poweredgraphicsprogramisgiveninthiscourse.Thiswasasomewhatproblematicdecisiontomakesinceexperimentalstructuredeterminationrequirestheuseofagoodgraphicspackage.However,WHATIF,thepackageusedmostinourgroup,hasatoosteeplearningcurvewhichwouldrequireustospendafewdaysjustforgettingacquaintedwiththeprogram.Thus,weshallrelyontheveryprimitivebuiltingraphicsofCHARMMtolookatastructurewhenthisCHARMMTutorial:1.Gettingstarted2.FirststepsinCHARMM3.Manipulatingstructures4.Energyminimization5.Introductiontomoleculardynamics6.Moleculardynamicsofhomogeneoussystems7.Moleculardynamicsofsolvatedbiomolecules8.ComputingNMRproperties9.Distancerestraintsismoreinstructivethanabunchofnumbers.However,ifyouarealreadyfamiliarwithoneofthegraphicsprogramsusedinthisgroup(WHATIF,RasMol,Insight,MolMol)thenthepartsrequiringgraphicscanofcoursealsobedoneusingthisprogram.Thismanualtriestoprovidealinkbetweenthetheoreticalconceptstaughtinthemainlecture(Vorlesung)andthedocumentationthatcomeswithCHARMM.Itassumesthatyouarefamiliarwithbasicconceptsofstructuralmolecularbiology,e.g.,thatyouknowabitaboutthepropertiesofthepeptidebondorthatyouknowsomethingaboutthepropertiesofaminoacids.(Whatyoufindinanyintroductorytextbookofbiochemistryormolecularbiologyonthesubjectismorethanenough!)Similarly,thisisnottheplacetoexplainthetheorybehindthemethods;however,practicalramificationsarementio