John D. Chodera

20 Pages·2017·14.43 MB·English

by  John D. Chodera

John D. Chodera
url http://www.choderalab.org
email [email protected]
github https://github.com/choderalab
ORCIDiD 0000-0003-0542-119X
twitter @jchodera
mobile [phone]
post 1275YorkAve,Box357
NewYork,NY10065
Educationandpositions
2013– AssistantProfessor,Physiology,Biophysics,andSystemsBiologyProgram,
WeillCornellGraduateSchoolofMedicalSciences
2012– AssistantMember,MemorialSloan-KetteringCancerCenter
2008–2012 IndependentDistinguishedPostdoctoralFellow,CaliforniaInstituteforQuantitativeBiosciences(QB3),
UniversityofCalifornia,Berkeley
Independentresearchfunding,sponsorsPhillipL.GeisslerandSusanMarqusee
2006–2008 Postdoctoralresearcher,DepartmentofChemistry,StanfordUniversity
WithVijayS.Pande(headofFolding@Homedistributedcomputingproject)
1999–2006 PH.D.inBiophysics,UniversityofCalifornia,SanFrancisco
Committee:KenA.Dill,MatthewP.Jacobson,VijayS.Pande
1995–1999 B.S.inBiology,CaliforniaInstituteofTechnology
UndergraduateresearchwithPaulH.Patterson(experimentalmolecularneurobiology)
andJerryE.Solomon(computationalchemistry)
Fellowshipsandawards
2017 SiliconTherapeuticsOpenScienceFellowship
2013–2016 LouisV.GerstnerYoungInvestigatorAward
2013–2014 GoogleExacycleforExternalFaculty
2008–2012 QB3-BerkeleyDistinguishedPostdoctoralFellowship,UniversityofCalifornia,Berkeley
2005–2006 IBMPredoctoralFellowship
2005 FrankM.GoyanAwardforoutstandingworkinphysicalchemistry,UniversityofCalifornia,SanFrancisco
2000–2005 HowardHughesMedicalInstitutePredoctoralFellowship
Researchoverview
Myresearchfocusesonredesigningthewaywedevelopsmallmoleculesforchemicalbiologyanddrugdis-
coveryandbringingrigorousatomisticmodelingintothehigh-throughputbiologyandgenomicsera. By
combiningnovelalgorithmicadvancestoachieveorders-of-magnitudeefficiencygainswithpowerfulbutin-
expensiveGPUhardwareanddistributedcomputingtechnologies,Iamdevelopinganewgenerationoftools
andopensourcesoftwarepackagesforpredictingsmallmoleculebindingaffinities,designingsmallmolecules
withdesiredproperties,quantifyingdrugsensitivityorresistanceofclinicalmutations,andunderstanding
thedetailedstructuralmechanismsunderlyingoncogenicmutations.AsacorememberoftheFolding@home
Consortium,mylabharnessesthecomputingpowerofhundredsofthousandsofvolunteersaroundtheworld
tostudyfunctionalimplicationsofmutationsandnewopportunitiesfortherapeuticdesignagainstcancer
targets.Usingautomatedbiophysicalmeasurements,wecollectnewexperimentaldatatargetedtoadvancethe
quantitativeaccuracyofourmethodologies,andgathernewinsightintodrugsusceptibilityandresistancein
kinasesandothercancertargets.MyworkmakesextensiveuseofscalableBayesianstatisticalinferencemeth-
odsandinformationtheoreticprinciplesfordesigningexperimentsandquantifyingerror.Iampassionateabout
openscience,disseminatingsoftwareengineeringbestpractices,andmaximizingresearchreproducibility.
JOHND.CHODERA-SLOANKETTERINGINSTITUTE-1
Publications
GoogleScholarstatistics:http://goo.gl/qO0JW
MyNCBIBibliography:http://goo.gl/e3kjgK
h-index:36/i10-index:52/citations:6906(18Feb2018)
∗asteriskdenotesequalcontributions
annualcitationcounts(GoogleScholar)–18Feb2018
SubmittedandUnderReview
Abl:TKI Co-Crystal Structures
Underreview bioRχiv
·
HauserK,NegronC,AlbaneseSK,RayS,SteinbrecherT,AbelR,ChoderaJD,andWangL
AccuratelypredictingtargetedkinaseinhibitorresistancetoclinicalAblmutationsusing
alchemicalfree-energycalculations
Weshowhowalchemicalfreeenergycalculationscanbeusedtopredictwhetherclinicalpointmutationsinhumankinasedomains
conferresistanceorsusceptibilitytotargetedkinaseinhibitors.
Abl:axitinib Abl:bosutinib Abl:dasatinib Abl:imatinib Abl:nilotinib Abl:ponatinib
PDB: 4WA9 UnPdDerBr: e3vUieEw4 PDB: 4XEY PDB: 1OPJ PDB: 3CS9 PDB: 3OXZ
(A) (B) ·
P1 DFrG-ouit stma2tes1 e34 8 AsWApHU6rg7715 sa2 inhnsgaoantScmoMmT∗ayr75b,5k GiTynre75e9a sotriaoghnkiooiufncGha∗es,meMoipglleernrooWmmTi,icRsse,cssuttrJouScu,tCsuhrfaooldberiroailnoJDghy,i,FabannidEtdSomePreosli+l?geecruMlarAsimulationapproaches,weidentifyasetofhumankinasesthat
2983765 areespeciaAspl7l29y promiscuousbindersofsmallmoleculekinaseinhibitors,andshowthataprototypicalmemberofthisclass,DDR1,achieves
DFG-in states thispromiscuitybyvirtueofitsmorestableAsp-DFG-outconformation.
(C) DFG-out DFG-out (D) WT
D671N
WDFTG-out DFG-inDDF6G7-1oNut DFG-in YY775559AA Underreview (kcMaUl/mEo l) 1.24 11..2251 0.79 00..8709
VersYi75o5AnFebrDFuG-inarYy759A16,201DFG8-insubmitt0e dRtou5f0m Eofl npfhotEs1rp00ho aFpte ty,ranM1s5f0e rreud / sre2c0e 0 tt2a50 JM· ,ThompsonA,LakeE,CyphersS,Albanese5oSfK27,HansonSM,BehrJM,ThomasDT,ChoderaJD,andLevinsonNM
AdynamicmechanisRmMfSoEr allosteri1c.a9c1tivation1o.f12AurorakinaseAbyactivationloop
1.87 1.11
phosphorylation (kcal/mol) 1.87 1.11
ThroughacombinationofFRET,IR,andEPRlabelingandlarge-scalemoleculardynamicssimulations,weshowthatphorphorylation
activatesAurorakinasebyanovelmechanismthatdoesnotsimplycorrespondtoaDFG-outtoDFG-inshift.
Prime Inrevision bioRχiv FEP+
·
PartonDL,HansonSM,Rodríguez-LaureanoL,AlbaneseSK,GradiaS,JeansC,SeeligerM,ChoderaJD
ExpeArnimoepnetnlibraryofhumankinasedomainconstructsforautomateEdxbpaecrtiemrieanltexpression
WeengineeralibraryofhumaRnekisniassteadnotm oarinnsowti tchlaussesfiufilcbaatcitoenrialexpressionusinganovelphosphatasecoexpressiontechnique.
131 S N R 131 S N R
0.698 0.902
Accuracy 0.695 0.899
n s 0 5 1 0.690 0.901 n s 1 9 2
o 0.727 0.940 o
dicti n 1 U7n6der8review bioRSχpivecificity 0.726 0.719 0.938 0.938 dicti n 0 96 4
Pre r 0 F3a1ssJ,Si9vakDA,C·rooksGSE,eBneasuitcihvaimtypKA,0L.e5im0k 00u.h.55le10rB,and0C.6ho7d 00e.r.6a68J6D Pre r 0 7 12
Quantifyingconfiguration-samplingerrorinLangvevinsimulationsofcomplexmolecularsystems
Weaddressa0fu.n6d5amentalquestionregardingwhymoleculardynamicssimulationworksdespitethefactthat0t.h8e4useoffinitetimesteps
Accuracy: 0.65 Susceptibleor Neutralor Resistant Accuracy: 0.83
leadstoerror i0nt.h6e4sampledprobabilitydensitiesandpopulations,demonstratinghowtomeasureconfiguratio n0-.s8pa3cesamplingerrorfor
animportantclassofLangevinintegratorswidelyusedinbiomolecularsimulation.
Figure2. Differentnumericalintegratorsintroducedifferenterrorstructureinphasespace,
illustratedinadouble-welUlsnysdteemr.Hreerve,iewweillusbtriaoteRthχetiimvestep-dependentdiscretizationerror
introducedbyfourintegratorsona1Ddouble-w·ellpotential[U(x) x6+2cos(5(x+1))].
RossGA,RustenburgAS,Grinaway⌘PB,FassJ,andChoderaJD
Thetoprowof2Dcontourplotsillustratesthedifferencebetweenthephase-spacedensityr(x,v)
Biomolecularsimulationsunderrealisticsaltconditions
sampledatthemaximumtimestepconsidered(Dt=0.7,closetothestabilitylimit)andtheequilibrium
densityp(x,v);solidlinesWindeicsahteopwoshitoivwecNonCtoMurCs,cwahnilebdeaushseeddlitnoesimindpilceamteennegtaatinveecfofinctioeunrst.osmostatinmoleculardynamicssimulationstomodelrealisticfluctuationsin
Thebottomrowof1Ddensiiotynpelontvsisrhoonwmsteimnetssteapr-odeupnedndbeniotmpeortluercbuatlieons,inanthdesilalmupstlerdatmearhgoinwalthelocalsaltenvironmentaroundbiologicalmacromoleculescandiffer
distributioninconfigurationspace,rx,withtheequilibriumdistributionpxisdepictedasasolidblack
line.Thesampledmarginasludbisstrtiabunttioianlslyrxfarroemshbowunlkf.orincreasinglylargetimesteps,denotedrDt,
depictedbyincreasinglylightdottedlines,forDt=0.3,0.6,...,0.7(arbitraryunits).Inspectingthe
contourplotssuggeststhatsomeintegratorsplittings(especiallyVRORV)induceerrorthatfortuitously
“cancelsout”whenthedensityismarginalizedbyintegratingoverv,whiletheerrorinotherintegrator
splittings(ORVRO,OVRVO)constructivelysumstoamplifytheerrorinconfigurationspace.
JOHND.CHODERA-SLOANKETTERINGINSTITUTE-2
Inrevision bioRχiv
·
WojnarowiczP,DesaiB,ChinY,LimaeSilvaR,OhnakaM,LeeSB,CaoMG,OuerfelliO,XuS,GoldgurY,MillerM,ChaudharyJ,GarlandW,
StollerG,AlbaneseSA,SoniR,PhilipJ,HealeyJ,VinagoluR,NortonL,RosenN,HendricksonR,IavaroneA,DannenbergA,ChoderaJD,
PavletichN,LasorellaA,CampochiaroP,BenezraR
Asmall-moleculepanIdantagonist,AGX51,showsstronganti-tumorandanti-neovascular
activity
Weidentifythebindingmodeofanewsmall-moleculepan-Idantagonistpriortoitsconfirmationbymassspectrometrycrosslinkingdata.
Underreview chemRxiv
·
GillS,LimNM,GrinawayP,RustenburgAS,FassJ,RossG,ChoderaJD,andMobleyDL
BindingModesofLigandsUsingEnhancedSampling(BLUES):RapidDecorrelationofLigand
BindingModesUsingNonequilibriumCandidateMonteCarlo
NonequilibriumcandidateMonteCarlocanbeusedtoacceleratethesamplingofligandbindingmodesbyordersofmagnitudeover
instantaneousMonteCarlo.
Underreview
·
IntlekoferAM,ShihAH,WangB,NazirA,RustenburgAS,AlbaneseSK,PatelM,FamulareC,CorreaFM,ArcilaME,TaylorJ,TallmanMS,Roshal
M,PetskoGA,ChoderaJD,ThompsonCB,LevineRL,Stein,EM
AcquiredclinicalresistancetoIDHinhibitionthroughintransIDH2mutations
ClinicaldoublemutationsactingintransincancerpatientsreceivingIDH2inhibitorsactthroughanovelbiophysicalmechanism.
PUBLISHEDANDINPRESS
NatureMaterials,inpress DOI
·
Kdye Kdye KdrSuhgamayY,ShahJK,TdsrcuhgaharganehDF,RoxburyD,Budhathoki-UpretyJ,IȷsikM,MizrachiA,NawalyK,SugarmanJL,BautE,NeimanMR,
pure/aq aq/np aq/np pure/aq
JohnsonDC,SridharanR,ChuKL,RajasekharVK,ChoderaJD,LoweSW,andHellerDA
Quantitativeself-assemblypredictionyieldstargetednanoparticles
Adecisiontreebasedonpredictedphysicalpropertiesandandmoleculardescriptorsiscapableofpredictingtheassemblyofdrug/dye
nanoparticlesthatcanbeusedintumor-targetedselectivekinaseinhibitortherapytominimizeon-andoff-pathwaytoxicity.
Dye in Drug in
Pure dye solvent Nanoparticle solvent Pure drug
NatureChemicalBiology13:402,2017 DOI
a L194 b0.4 CyWWp12h ++TTeppxx22r ((s(cid:111)(cid:111)==11S74..83, nnRss))uffcE,B40ehrJM,Chodde2350r0000aJ3D0 nM, enazymne cdonceLntreatiovni·nsonNM
eKinase activity (RFU/min)1102257055050000002 nWpMhT oeWsnzpQy3hm1oe8r 5ycMoMlantcWQDeedn1 1Kt 8rS(aW51tiLio6Tmn)2uflaNormalized activityWKinase activity (RFU/min)Qt00112345i2...1E050o0000000000801n058Q1u- n11(cid:43)p8Mh5+oM es1np0zhQy[o-Tmr1py8C (t)xela+25 QQCQt]cL(ey(cid:43)11o120ds88M8n0 -55.5(lcQ)iC20MLCtee- y1N ns80t+-5-rl+TaiTAACIdArkOaNtetppTNi3)oxnpx0en2x2l2 t i5evltalc0oWWnelcleget12oKinase activity (RFU/min)hisv r--o1uakdTT1234wt0app0000y0oxx5e0000r22ns0000Tn0i rf((iedp0m(cid:111)(cid:111)fi1e==eci5es95WcH0 ..er(Cr492mnTc ep nsnn3AhaMoA),ss2xtoh ))a0esrimnco0p,zQcghyev1ttmoWr8rec2ei5ym ei5ocMvleoa1a0tonta5ecsanaexdnidnn e(tntQrcW-+Correlaion time (ns)baTcT1tagciiTpo8pax)123onoe5xw2o000L205B es lrnl0nixe,WBhncmadWbL1Kinase activity (RFU/min)WTieishyteeou1112(n025p257eWtoQ050505aTaln0000000rH1zat1oif38aprW0lyQ5nbl zny,agL21xM-)8m SpW oQ5e-+ygcy2hTmCnT11ozhpNpl3y8xgsWexmei4.2mp52ae1 xsh2M r scoehomesrCnyKinase activity (RFU/min)3cylleaegsadnHt-112letpi3r050:5tadade000cx0st 4i000(0io,0Cntutr1105yaC050Cues9a000n-y-eo000lspi00att-thesl4io)t+treedesipomm,hdoduQ2r-syo1uel8auc5t0n+ehhMldara t(y1Cpyt-yidQ-sFir7-o1ldoi8rito+e5so)LnTnrn·ipgxn2todD eaogangilnyfOtaeaessLnIeioC-mn,2abRpnF-ulodoehslntmpdyeriddnanoblgtranou@otnreehgxatdoAtywemiSogh,neoylSudrsaretrltkaavoahetggeareSolnae,Gafavtfsueseeeuncrtnrtuspnehn.rrdsirsMeoianrRgulg,ollgCoyshhsshotitaadfetbelsrrlteiaienchJrsDyuand,bcCarsotrttgoirievasvnstaeeJbtRuosi,tonuaildnnibzdnasiTetntihtorwoAnamottruphkesraouotunnhrsdCaaeeBvrelbiehysigh
JournalofChemical&EngineeringData62:1559,2017 DOI
·
MatosGDRandKyuDYandLoefflerHHandChoderaJDandShirtsMRandMobleyDL
Approachesforcalculatingsolvationfreeenergiesandenthalpiesdemonstratedwithanupdateof
theFreeSolvdatabase
WereviewalchemicalapproachestocomputingsolvationfreeenergiesandupdateFreeSolv—themostpopulardatabaseofhydrationfree
energiesofneutralmolecules—withmorecomputedandexperimentalproperties.
Spine Spine
PLoSComputationalBiologyHM13:e1005659T,px22017 DOI
EastmanP,SwailsJ,ChodeC-rhealixJD,McGibQ1b85onRC-Thel,ixZhaoY,Beauc·hampKA,WangLP,SimmonettAC,HarriganMP,BrooksBR,andPandeVS
OpenMM7:RapiddeveloWatpermentofhighperformancealgorithmsformoleculardynamics
Water network
network
ThelatestversionoftheGPU-acceleratAeudrAmolecpuT28l8arsimulationOpenMMfeaturesavarietyofincrediblyflexiblebutfasttoolsforrapidly
PKA
prototyping,evaluating,anddeployingnewsimulationalgorithms.
JOHND.CHODERA-SLOANKETTERINGINSTITUTE-3
PLoSComputationalBiology12:e1004728,2016 DOI
·
PartonDL,GrinawayPB,HansonSM,BeauchampKA,andChoderaJD
Ensembler:Enablinghigh-throughputmolecularsimulationsatthesuperfamilyscale
Wedemonstrateanewtoolthatenables—forthefirsttime—massivelyparallelmolecularsimulationstudiesofbiomoleculardynamicsat
thesuperfamilyscale,illustratingitsapplicationtoproteintyrosinekinases,animportantclassofdrugtargetsincancer.
JournalofClinicalInvestigation126:3529,2016 DOI
·
XuJ,PhamCG,AlbaneseSK,DongY,OyamaT,LeeCH,Rodrik-OutmezguineV,YaoZ,HanS,ChenD,PartonDL,ChoderaJD,RosenN,
ChengEH,andHsiehJJ
Mechanisticallydistinctcancer-associatedmTORactivationclusterspredictsensitivityto
rapamycin
WeusemassivelyparalleldistributedmolecularsimulationsonFolding@hometoprobethemechanismactivatingmutationsofthemTOR
kinaseidentifiedinclinicalpopulations.
bioRxiv preprint first posted online June 29, 2015; doi: http://dx.doi.org/10.1101/021659; The copyright holder for
this preprint is the author/funder. It is made available under a CC-BY 4.0 International license.
￿
￿￿￿￿￿￿￿￿￿￿￿A￿￿￿JWfC￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿oitrtdNnf9ouo￿onoooih￿0fnsoemerrirO￿nmttl↵e⌧�nyee(itu%cosnvAd—ghmurˆ￿eftegme￿oe[El0aw0t%irnpdrnq￿rii,saf(fopToi￿bt.aelwxeorelmt]l￿n%clraeees?ea￿froRtecddvrcedrrathMc,ae-Frksha�eotscaleilS0a)Arhcghlsnalˆeiy(rwitpuonifesz)ceaelicerutaeoidraalvetroirltmseJhasezwdiouownioan￿ltsantlrpienDtncdth.agfiagcehoesoueftHoomyr—tinndesismnhonh(icdttatlne￿wt(raChtypatreatii.hameedomao￿obrwtdvvreen￿heseueeaegd￿siahoroldsmmlr￿lyrivl)arfneo￿.ietdeoplateeuhr±eleWgmefolbsreefeisrwr￿eieoohmxoretss.eemrfniie￿rltttloxnei￿tedrh￿pnodhprac.ad￿￿eftieietths�nhs￿ie￿id￿nchlsnAiiegˆ￿.s￿ttcoaf￿geeity[)rcag￿matdtr￿odot0i￿raiolen0￿s,mdi±teT￿fnodasgaeteaq￿t]sio￿gkdm±a￿cerudc.ynoem)nh￿lp￿loi￿.uelgo%dip￿imae.mcbiw￿aedo￿txvTprp￿crriln￿ieaneedfmfoa￿￿dotrgdnrdi,￿rrriehoesgzoooafmet￿ridneeo0rrt---,oearloucarthiyuotonat.noaudmtCoamotmaetpidcuaetllaqytduioeitnleibr1m2ria:n1tin7iog9tn9he,d2eeq0tu1eil6icbt·raiDotenOdirInegimonoolfeacmuolalercuslaimrsiumlualtaitoionn,salongstandingchallenge
￿￿￿ DISCUSSION
￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿Fvlaop((artcbaijbiposc￿sthemwtadwttsmeearhuoiihoeionerfy￿￿liovaeaIomfcmcnhiaovisenineulrtGaalinnsBn￿mreveztsnegesztlhesnstonbidelsituridtitc-irityvcb.rurleinrnatintetvrracaai?eohbaantolzeeaeahtesyilnadgtagggnitxses3bilfabgmpiasivTd’rienrdwnesttoioda-s.ubEcbutkipdlemlf,ivfaagentfuhioodekfeercitvnm=otilociaarcaanrohayrntrsieiatenodiaoiorbhdsoz￿soicrtnhmteBssspgrvtf2aterieoiwamieoindmmeituamaeiaiseaiaaiwc0aat.csaqraecNtsnvcstslhatns0aneeatiahafpserviitinhuidtcUiulsaeato0oltnowqtnn-toceiridhloaogiithvanineetsd⌧enl↵etdvnlnugtvicieaghihilalitsmnocdsve0acanklabetgiitffeftfpetreydetoteeolouhrrloiogrnrvielrii(hurs,ioerqiodonsis￿ebraaa0taaefovroqaneec￿i(iminumttnbnriretnsfismhaaewd(idus⌧￿hehinatiifotrcbcFaoiemeaoiloiu0￿sae)atrerirttecemineuflqnirtsiourcerfbinaiatgltiaooredahmotoeulurciissrophttlecreuaslu0t,endr￿leaeietnilrra(fkliytygaqmml⇠ytpplagiirriianoi(i.rtaaxcnmifoesecebustfilt-lldoiomdonueearoimuaitxtaednroiodirHc9emenandlieitrlspf￿rairllnaiaeoptuivpe0osgot(sbotgvteaeeioaetn1eytinintlniainsenc￿rae⌧iwtcpntdioss0qsi8sguvdaihc,ohg,leiotmtctt)eutntluomu0laabsta0r.s￿uoefpiheeieotomwirric0imoatntruoatImmie)lauwemeroeeuuitfriaciiarlteoiaenlambrp⌧delsofsslsilatrlusapsmyennelcd)bhrnrflilt)aof⌧itoteelijyna.ibenipyi)ngtecveadeteaicelxi)ms,blvmthanigchaaeatsrcetAeeersseeleizctceoa0yicoeainlettrseacsa￿0oad.Eeotomliaeoicrwrspntyndzbteagrnttirqmiit)nsorebibalcc?iseeritsanrc[heostyizsiotwetmdhhcme￿iitimpqse,ecae0tarsnoamebsi￿Waonodaeeeeae,xudotttsp.opnsTaitbpdnifhacsi,rrewnimbiecnhmtofsseancu]eeln,dedelaToee0,ieoeteep.enbsoeyltbtatiar0cnrlqFadtsndlathgDendsawealtrxyrrog,hislieetdtutv0rkmddnjaiagiionekfwmhteeieonesmaled,armiurtttrnnesfcldvweaogeiogroiliasswo[rpirotipjosactolaabettteezneomthvtso￿￿￿￿￿￿￿￿u￿ctra￿ehwfgwti0cin￿t￿￿￿￿￿￿￿e￿rvtrr￿seorbte￿￿￿￿￿￿￿￿￿et￿ri￿thdaeaccea,iauiasmhgnfthegileearartia1aqoitosbaewuetTett0anmmslthethnNadgyb0msfauti.ntenlscd0t.aiotisgerntemieepeoi�teneo]ihercoiognBcecpgo[evaaot——Bonrorrcfadnsr4iin￿iinh↵uleenehleyg0eeeeyssstssssr.￿t--tf---eft,windt,aho,h￿diliancDiot￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿u￿￿￿￿￿￿T￿￿￿￿￿￿a￿sRdJMwpJBMTlt￿￿￿￿￿￿h￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿s￿￿￿￿￿￿￿￿￿￿ig]pni￿￿￿m￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿e￿￿￿.oniioictlseuegentmtatibrtpbepotaoatfgcnepuvgseoootpsnHoc￿teiihhhinueoarcvaeooessllbapfso?iiiemoototoilotaAparaslriqrreeettasrinTAAeayrsrtioozsttIanniicrnilliisnsslincyeiuhcfselilitopemmqluuaoncoehlisaesrtos.omawisi,lghtlctaeerstbPioiortdraohsitrtuutbpetsomitywritramemS,eleaaflualsyerteos7nslnnecmeateim0lilsutemtaohcentgirstdkietlttytesspotirrrfrdhlehsmu,iisooseetehmtogiliogenddcaaeirobesiooagleaotraseoontplilddegtuilefhsivrcpsnasanvidr.ePmennoiheqpofcpcanipeadflcntatantscaeiatgnretacda4ebahccysatxdlufilesapwoiiecotiotaerlxmmrhoheebfuo[lruesucatiatiolccidxatiluipsotnederdrnlidnmyhrolnairtitulslaamemampt0ynpeeeaiittieaa-eurfsi,sctpbroucvbonnn,ecoasurch,o,uohawacttlep—rreiturheaioborhltctbcmarnrlTicicdusrsttwsectcyoimuOahnaaidaennoelyalludlfewelifierlhiataieedtrrAhony]mwtnmsttttfiruiyasbyrgpreonee—nilariioscadsneehieifdPnenrieoozeeegnffnnoortd,trettcacuenoeeloodtvraSlsewh.ieIifdeloerrsrtnheaaignsdronerorooosst.lfnclfeiiIsItwesuatt￿iunpaalgomerAiMetwruhvpfMfmsibvsncoofsstucbtavlntfebnstnAttileeaiaspmiileffasiehioheirebcwhUmngileinlwinsMiormserrabwfyaiorsplcdcreeteoilsrowdhsiytnutdgLmipacdicteeohfbhieinistrtrintheac.chuKreohue￿iaArtolosrvgeetgnnheSiveCPdaeeeohkrarnhAoenneasaetTtwsc.ltsrlianaswiidfceprnbe￿sndcsbi—eaEsisedplecrnotsIneiepmrfioreosmyitronGlttOetlro,—odreetiiqatAeds[waetrrohgnewiymehczbraleettrpu￿nwlthmssumraNltauro.easecaihwchtn￿ae.pwjeeeee—rDdoeutaiydcehbueptglfco.]F￿ngaitrriseuresuoDraa.aoeeshresehe￿oecd,hstsrulsse(pixbnstornvhsslOsodytnpEiegaraseumtpadtiuiiaauuwoauprlcoieumilmotaoaoecaTyaotcBevtocadmnvcciesltarootna￿oaaoxlwueamrtvgAssirhhap￿kianenpede----fanlulaotsyntiraaapaobIriatphgcosseintcisldLtplglchnemilselslyoylrnuaahttieeeerioelcSlseiapodrteaitccsiiha.nyossbtsetrtmoeebiamipsonc,nahwceiocbhtceiacwthltotnHannialhffarest:cahnmarmlcfcpencreond,tneumitsctginhoyleeodlhtasahseerrtth.xirdairecsktwaioorhhofEmnatntiqdpvieonetIo—oittdblnimenionqtelrociaeuaeitnyfcettsrtmaeaceeesioho.Jzvirpetwirdtn￿cltGtlsiastndoqqlaiouhe￿s—meeiraiieehcmoeeilasieJa￿blzntauuedcceeMrtsyhhntmelhrdfitinl,gfp.CHjireiiaeetenlmebeseeemell,eaia,soiurciipvwnruihsuoogshncnrmxebbnenttmttanattpemtrctmibtLp￿atwchcirrltaviseiolmoitnehw,fhmaahn,￿eiyilwwiithr.r—htdnAarsstgo.ottieeaaciiedayhotyegohetuRtaiiieebiuirtmcnntoooaalanehixncsnaorrrmaegalcetiioliddnnnnngeeeeeeessatt------)flmyieudsxdmBsfidsmaie,fteebciOerdsnlvaudneotrelnebMsrtlnmmiwoyuat-cpoyroiwrBngehdlctaeeAehac1hmcnDlrSati9ueein,,lteawlBl9MigeacTrran:atpor1ykhegdlbrlDc2eyotileihoenteC9asyroncsgstI1mciD,oiqrpogK2moLuialnorb,,etfrpo,a2oMtsueun3ao0nimtdtn0tfelL1ieCeort:poi9-ha5hndrmgnseeo4uKau·ddSi5i,rcDdtieAseac,aoernttMc2Oaidideynac0JPrcCgfIDruL1lfifhofcg5ro6ohcehddeerei·exixecevseeDariennarnegceOfinJetirDs-,sgewebI.i.fleuadosttesotrrhf:tdetNhribsaeteenrnsiaSbcfetuhArtmlibMioaqenrtuPkwcioinLedeeg5fnfidaccnaeiqdhenuniamestlsoilptuferoisoner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￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿ashpcdadteocdtStiAuehmbFhlttfbaleeoeeaeoeeuiMnrEIeOaannnctmnvGnceeerraitmxornssgius￿nteadm.sadeiapptiiFrf-inrtttosdh￿vipntxiBeurreeiittceyyecuiasgia:fepsrihhognotrraCarenebri.poMwponaciclaeelsmnlCemlfatea￿colrtltemgricrsieemefat)nehu-riebutnucetpefeerypiaahudaoaisierfczteislaeanroneotors[eartatritrubrttsnec￿ctinhiuiviranoftwtbecgcafloiinerot￿thisabueoarnrtGxoarriislne.tc￿r.oelarorosrritpt,oleinAAoelwstshletd.tfnobirunenKryhusnyFtnesskatrarfCWlpyer.we(,eFtheossoehtitiwoTsuioewPmrtn-e￿opeeetcrasyaAtalafhrdrh￿llhddiIfktroaisbeveo.rrcefknVsltae￿eyimoieeeebtrehachau.oentmstnfrrticpsrsyt)iorcvKascsbetmoMdincfuestsmpeaniuupeoroldc]tiedDsdavdlncannlraitoFrdsbefherfa[neeIroheiapssocgscidii￿MctSdinsedegengrdlstfcevgaioelb￿tteCsaioilmgwonl.aeLeiraeidneeftedse]ncUntnemnti￿thidt.d)lnleareechitaattdeegS￿ddcp.refunvestrtlolaTaitaaoodcSayd.aiinvrsrse[dder￿faxaethlcterrI￿lieaersiotrrrOie.tecb￿lltctidsdtsyoem￿fbleihssnihaFssrhuyciul￿Npeeip]fucnleredegocceiierecs(erocblwttomzgsesatresatarrhshrcoplefrositormoicvaiir,p)i.an/idpietctnresge.ymaeirtirerShseroaecrnessshlgemesclcSeeddoiesmenttnacnbeoecrcasideadaievmcempltitmouaronlcuns3rtenedeistoabSonpcrehocmsra.drudctteecanoiouyelttsrifaoyesaailAanvktaceeov;cnasrasneumvresdsaysnaedfrottsttgcbsplaouairilavteirtiaatfi[ctotmisoezoe(issrrta￿qhnimi(utlntuGsneeeimstnarreise￿ceupidyarlaasitsmsgAaobeamnIa]eiiwsraat,tIh.odmrxFmelbicItgrheratleccpaatensroFdBdyelneaeoee,trmmedibwdirtenota/ei￿ci.rrinseetr--------f￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿iefmcpcwpmnttuerdorhcsa✏oppcwiwfCtieccactsttiiaaehiheooooohhnllrnxeffiaeolioopy=ehhCeedeetoommetrisrennnnnAaaRIS,ltnvdlilso1rphlocciinvdtlunsaalnlwdlaccrrestsstueetee.eeclitta-4ea2ukitaggdrrrtt0entithhhksrrnccppolcette,siiuaphd.taaepgceeiyiidsobzueecetne2cucnt,apccrmwrsyhnneehCosssrcaaeerrehrncudotn,tfoilrseoi.uraiiattscooitehcencpnhasptfiHMchAcCIJnaHttezznsrewnss,insneeosonro.et.raaofaemtaylorlgurHsdetgpisoaayoasCenfna✏nfsgnleftmndtenbfilnaoc,eliibtorotesOrs,eciierseoustyssftdolgeblxolacuiaerseatarettrct3tmrwecfpecitsf-bnewcracleoiennanrconeeroafstt,eetyouanooetiosooeideednoedcernaeymdrotnnra,ooisrusmCgffnrsntusrnvof-yccmmr[dttot1ftirostCsmepuiccscmtr￿,reemdelftm.iyenemeHtt.madetf￿oecsrihrrhbboilmxo0ldpreCcrclhtooTcoeopletdrsi,,fietm,da2alaeeyfe5hlaenipieooielhfumhclddtmmeonlscnCeyrttmseol.￿d4nlc￿tiotpeapfepoltgrhdbhuthtueenplaotched,t￿oorhlitoda.rhplpukeopwiTeseacns✏2t￿ncoasunanise]rysmrbatlswheicoritn,.evlihreMgcrettfrfli,c.fftntnnepvromc⇡gnabaoaecroseiunaeiepeutiwopchaeivzaCe,aoftgosoteosorctomtyrlrfnsuxlooiaroonohoHoamilciiaimssstnsonkCttcdbslbe2tplrablnddcehulaephecltheeeota,ttitnm-iliileaelooieiltmbdfethehnoesnrdhcermpe(semvpaflwnrl4iatehCFoinnli,nle,ayiieaolodeoetohbrtagpszeubreeaieaetiawiasebltyllrtHefsxgnitlalseturoDpdlllcllnov,opanto,zevban,ldaetatuerase.gb-lcattlaes3ei-iihxrleenaprtygdpwitchyiinetalttro￿oinninCiqcrtrtptlicnlssei[eietlrztorsiCccg,)mireehntaowcthhi￿ttgrghpoduaro.asntlvhhhlesceiresnoot￿ae.oiHdihyamoactpnoayi✏cnbaaenprseWishetdiha.rfssa,obensri-dstidnrrrnrlCoaheeacecfa.snAIWt￿meiiqmitianvnh⇡asdaursnnaelcoeolaeul,ysnssjc￿tleieelueuseimmefTorhetnyq3mfeaasslnsuweenlofo]orqdticyceimiempihrimen.nytutablatsshvodw1eiiacoorttfueuepheceretncgsMeaeinhrdntcysolfbmjnlftemosacdeoctdneihonfueeedohrwpieticmvgseoetootsPponlnsprfoo:sdafairxorehueroiooietsosrkirtofinoetccncCfooupiddoeertlttiehbsintcoerirbdpeonydosuicbyrmrgfflnnelinohvtcCneureeoiredinetecseoneimcfeexceccdsfcetoo,ddorttrteicalusrphqfashflltlshemhtfeerehasre4iaonuiif[irolnicalctouCytasi✏doieeeenliac￿etalevcasrnfrhzdoDtooluy:tmlheklltmivgloed￿etrgHhifalanerreeszdam:rppnmtniro=ccetiaafctedf]nimqreiatyocchtoosrtiC￿ooooccrratusnnsxnspogohttetttbppluedornchemmiiedduiierrhthhilgglcennnbqonalooaaeiinre2eiiii3siierflliiddeeeeeeeccccrsssstttt---------------ffnl,,,,otsmmcodoingcerab2dieafrsto.ys2ltuurepCtc:scoh1heeheeRfiyd–eseGls8amtilco,dcp,Vaiks2dsler.eotp0normfre1ydohto5tpiBuingeS,hs·cr,t1-tDtFrqya1iiunodOt8aleaenl:tyIti6tahoLy4eWinmf6pSLao6a,n-tcL–e2huI6nUi-nCt4HPieha7A-alyrC4ofeod,-a,sJrd2rtuaaaod0lnbtkx1edlienyr4ansprg.aAdhWltRyuXivs,MtieiRlcalusaLiutralfeabpomnsrrtbotmeCrupaare.tgtreS,AtcwyuSasd,onaGagpertelaienimsbaFeywitensiasas.yottWcPesiBecttrh,hsaCehrtshoeiefowdtdreo·ehharoDyadwdbJOrDltooh,IgceCkerNnsoaaIsSsnsTedJ-sRcru,ueanrvnadedteaerTldihhsToysumhpeoepsmxsiwoconiMtChLB
SivakDA,ChoderaJD,andCrooksGE
Timesteprescalingrecoverscontinuous-timedynamicalpropertiesfordiscrete-timeLangevin
integrationofnonequilibriumsystems
Wederiveasimple,easy-to-implementLangevinintegratorthathasuniversallyusefulpropertiesinmolecularsimulations.
PhysicalReviewX4:011020,2014 DOI
·
PrinzJ-H,ChoderaJD,andNoéF
Spectralratetheoryfortwo-statekinetics
Wepresentanewmathematicalframeworkforunifyingvarioustwo-stateratetheoriespresentedinthephysicalchemistryliterature
overmanydecades,andprovideaquantitativewaytomeasurereactioncoordinatequality.
JOHND.CHODERA-SLOANKETTERINGINSTITUTE-4
JournalofComputerAidedMolecularDesign27:989–1007,2013 DOI
·
WangK,ChoderaJD,YangY,andShirtsMR
IdentifyingligandbindingsitesandposesusingGPU-acceleratedHamiltonianreplicaexchange
moleculardynamics
Weshowhowboundligandposescanbeidentifiedevenwhenthelocationofthebindingsitesareunknownusingthemachineryof
alchemicalmodernfreeenergycalculationsongraphicsprocessors.
JournalofPhysicalChemistryB117:9956–9972,2013 DOI
·
WangL-P,Head-GordonTL,PonderJW,RenP,ChoderaJD,EastmanPK,MartinezTJ,andPandeVS
Systematicimprovementofaclassicalmolecularmodelofwater
Wateristhemostimportantmoleculeinbiology,andaccuratetreatmentofitsinteractionsiscriticaltoaccuratemodelingfordrug
discovery.Whilepolarizablemodelsofwatercanachieveveryhighaccuracies,theyarebothdifficulttoparameterizeandexpensiveto
employ.Here,weshowhowahighqualityinexpensivepolarizablemodelofliquidwatercanbederivedusinganautomated
parameterizationengine.
PhysicalReviewX3:011007,2013 DOI
·
SivakDA,ChoderaJD,andCrooksGE
Usingnonequilibriumfluctuationtheoremstounderstandandcorrecterrorsinequilibriumand
nonequilibriumdiscreteLangevindynamicssimulations
Allmoleculardynamicssimulationsintroduceerrorintothesampleddistributionbyvirtueofthefinitetimestepusedtointegratethe
equationsofmotiononadigitalcomputer.Whiletraditionalapproachestoanalyzingthiserrorareextremelycomplicated,weshowhow
interpretingfinite-timestepintegratorsasaformofnonequilibriumdrivingleadstosimple,straightforwardschemesforassessingthe
impactoftheseerrors,aswellascorrectingforthem.
JournalofChemicalTheoryandComputation9:461,2012 DOI
·
EastmanP,FriedrichsMS,ChoderaJD,RadmerRJ,BrunsCM,KuJP,BeauchampKA,LaneTJ,WangL,ShuklaD,TyeT,HoustonM,StichT,Klein
C,ShirtsMR,andPandeVS
OpenMM4:Areusable,extensible,hardwareindependentlibraryforhighperformancemolecular
simulation
InexpensiveconsumerGPUspromisea100-foldincreaseinsimulationpowerbyproblemsthatcaneffectivelyexploittheirhighly
specializedstructure.Here,wedescribethelatestadvancesinanextremelyhighperformance,open-source,extensibleGPU-accelerated
libraryandtoolkitformolecularsimulation.
BiophysicalJournal103:1490,2012 DOI
·
ElmsPJ,ChoderaJD,BustamanteCJ,MarquseeS
Thelimitationsofconstant-force-feedbackexperiments
Popularconstant-force-feedbacksingle-moleculeexperimentscancausesevereartifactsinsingle-moleculeforcespectroscopydata.We
demonstrateasimplealternativethateliminatestheseartifacts.
ProceedingsoftheNationalAcademyofSciences109:3796,2012 DOI
·
ElmsPJ,ChoderaJD,BustamanteC,MarquseeS
Themoltenglobulestateisunusuallydeformableundermechanicalforce
Wemeasurethephysicalpropertiesofthemoltenglobulestateofapo-myoglobin,andshowthatitisunusuallydeformablecomparedto
typicalproteinnativestates.
JournalofChemicalTheoryandComputation8:3445,2012 DOI
·
PiteraJWandChoderaJD
Ontheuseofexperimentalobservationstobiassimulatedensembles
Weshowhowtheconceptofmaximumentropycanbeusedtorecoverunbiasedconformationaldistributionsfromexperimentaldata,
andhowthisconceptrelatestothepopular‘ensemblerefinement’schemesforNMRdataanalysis.
Science334:1723,2011 DOI
·
KaiserCM,GoldmanDH,ChoderaJD,TinocoI,Jr.,andBustamanteC
Theribosomemodulatesnascentproteinfolding
Usingsingle-moleculeforcespectroscopy,weshowhowtheribosomeitselfmodulatesthefoldingdynamicsofnascentproteinchains
emergingfromtheexittunnel.
JOHND.CHODERA-SLOANKETTERINGINSTITUTE-5
PhysicalReviewLetters107:098102,2011 DOI
·
ChoderaJDandPandeVS
Splittingprobabilitiesasatestofreactioncoordinatechoiceinsingle-moleculeexperiments
Wedemonstrateasimpletestforidentifyingpoorreactioncoordinatesinsingle-moleculeexperiments.
AnalyticalBiochemistry414:297,2011 DOI
·
TellinghuisenJTandChoderaJD
Systematicerrorsinisothermaltitrationcalorimetry:Concentrationsandbaselines
Awordofcautionaboutlargeerrorsinisothermaltitrationcalorimetrymeasurementsarisingfromligandconcentrationerrors.
JournalofChemicalPhysics134:024111,2011 DOI
·
MinhDDL,ChoderaJD
Estimatingequilibriumensembleaveragesusingmultipletimeslicesfromdrivennonequilibrium
processes:Theoryandapplicationtofreeenergies,moments,andthermodynamiclengthin
single-moleculepullingexperiments
Wederiveanewestimatorforestimatingequilibriumexpectationsfromnonequilibriumexperiments,andshowhowitcanbeusedto
estimateavarietyofusefulquantitiesinsimulatedsingle-moleculeforcespectroscopyexperiments.
ProceedingsoftheNationalAcademyofSciences108:E1009,2011 DOI
·
NilmeierJP,CrooksGE,MinhDDL,andChoderaJD
NonequilibriumcandidateMonteCarloisanefficienttoolforequilibriumsimulation
WepresentasignificantgeneralizationofMonteCarlomethodsthatprovideanenormouslyusefultoolforenhancingtheefficiencyof
molecularsimulationsandenablingmoleculardesign.
JournalofChemicalPhysics134:244108,2011 DOI
·
PrinzJ-H,ChoderaJD,PandeVS,SmithJC,andNoéF
Optimaluseofdatainparalleltemperingsimulationsfortheconstructionofdiscrete-state
Markovmodelsofbiomoleculardynamics
Wedemonstratehowmultitemperaturedatafromparalleltemperingsimulationscanbeusedtoconstructfullytemperature-dependent
modelsofthedynamicsofbiomolecularsystems.
JournalofChemicalPhysics134:244107,2011 DOI
·
ChoderaJD,SwopeWC,NoéF,PrinzJ-H,ShirtsMR,andPandeVS
Dynamicalreweighting:Improvedestimatesfordynamicalpropertiesfromsimulationsat
multipletemperatures
Wedescribehowreweighingtechniquescanprovideoptimalestimatesoftemperature-dependentdynamicalpropertiesfromsimulations
conductedatmultipletemperatures.
ProceedingsoftheNationalAcademyofSciences108:4822,2011 DOI
·
NoéF,DooseS,DaidoneI,LöllmannM,SauerM,ChoderaJD,andSmithJC
Dynamicalfingerprints:Atheoreticalframeworkforunderstandingbiomolecularprocessesby
combinationofsimulationandkineticexperiments
Wepresentanewframeworkforcomparingessentialfeaturesofthedynamicsbetweenexperimentandsimulationtoidentifythekinetics
processescontributingtoindividualrelaxationtimescalesinperturbation-responseorcorrelationspectroscopyexperiments.
JournalofChemicalPhysics135:194110,2011 DOI
·
ChoderaJDandShirtsMR
ReplicaexchangeandexpandedensemblesimulationsasGibbssampling:
Simpleimprovementsforenhancedmixing
Weshowhowasimplechangetothewayexchangesarehandledinthepopularreplica-exchangesimulationmethodologycan
astronomicallyincreaseefficiencyatnoincreaseincomputationalcost.
JournalofPhysicalChemistryB114:2549,2010 DOI
·
PonderJW,WuC,RenP,PandeVS,ChoderaJD,MobleyDL,SchniedersMJ,HaqueI,LambrechtDS,DiStasioRAJr.,Head-GordonM,Clark
GNI,JohnsonME,andHead-GordonT
CurrentstatusoftheAMOEBApolarizableforcefield
TheAMOEBApolarizableforcefieldisabletoreproduceadiversesetofphysicalchemicalphenomenontohighaccuracy.
JOHND.CHODERA-SLOANKETTERINGINSTITUTE-6
JournalofChemicalPhysics133:105102,2010 DOI
·
ChoderaJDandNoéF
ProbabilitydistributionsofmolecularobservablescomputedfromMarkovmodels.
II.Uncertaintiesinobservablesandtheirtime-evolution
AsimpleBayesianapproachforthemodelingofstatisticaluncertaintiesinkineticandequilibriumquantitiescomputedfromMarkov
statemodelsofbiomoleculardynamics.
BiophysicalJournal98:3062,2010 DOI
·
AdelmanJL,ChoderaJD,KuoIW,MillerTF,andBarskyD
ThemechanicalpropertiesofPCNA:ImplicationsfortheloadingandfunctionofaDNAsliding
clamp
MolecularsimulationsofthePCNAclampresponsibleforDNApolymeraseprocessivityshowasurprisinglysmallenergeticpenaltyforthe
deformationrequiredforclamploading.Featuredonissuecover.
JournalofChemicalPhysics131:045106,2009 DOI
·
BacalladoS,ChoderaJD,andPandeVS
BayesiancomparisonofMarkovmodelsofmoleculardynamicswithdetailedbalanceconstraint
ABayesianschemeforcomparingstatespacedecompositionsforMarkovstatemodelsofbiomoleculardynamicsthatincorporatesthe
factthatphysicalsystemsmustobeydetailedbalance.ThispaperutilizesrecentresultsfromMarkovchaintheoryonedge-reinforced
randomwalks.
JournalofChemicalPhysics131:134110,2009 DOI
·
MinhDDL,ChoderaJD
Optimalestimatorsandasymptoticvariancesfornonequilibriumpath-ensembleaverages
Wederiveanoptimalestimatorandcorrespondingstatisticaluncertaintiesforinferringexpectationsofbidirectionalnonequilibrium
processes.Theseestimatorshavewidespreadapplicabilityinsingle-moleculebiophysicalforce-spectroscopyexperimentsand
nonequilibriummolecularsimulations.
JournalofChemicalPhysics129:124105,2008 DOI
·
ShirtsMR,ChoderaJD
Statisticallyoptimalanalysisofsamplesfrommultipleequilibriumstates
Wepresentahighlygeneral,statisticallyoptimalapproachforproducingestimatesoffreeenergiesandequilibriumexpectationsfrom
multiplesimulationsthatprovablyextractsallusefulinformationfromthedata.
JournalofMedicinalChemistry51:769,2008 DOI
·
NichollsA*,MobleyDL*,GuthrieJP,ChoderaJD,andPandeVS
Predictingsmall-moleculesolvationfreeenergies:Ablindchallengetestforcomputational
chemistry
Ablindevaluationoftheaccuracyofalchemicalfreeenergymethodsforcomputinggas-to-watertransferfreeenergies(solvationfree
energies)ofsmallmoleculesdemonstratesthatmodernforcefieldsarelikelysufficientlyaccuratetobeusefulindrugdesign.
JournalofPhysicalChemistryB112:938,2008 DOI
·
MobleyDL,DillKA,andChoderaJD
Treatingentropyandconformationalchangesinimplicitsolventsimulationsofsmallmolecules
Anquantitativeexaminationofhowmuchconformationalentropycontributestohydrationfreeenergiesofsmallmolecules,with
implicationsforligandbinding.
JournalofPhysicalChemistryB111:13052,2007 DOI
·
ShirtsMR*,MobleyDL*,ChoderaJD,andPandeVS
Accurateandefficientcorrectionsformissingdispersioninteractionsinmolecularsimulations
Weidentifyamajorsourceofsystematicerrorinabsolutealchemicalfreeenergycalculationsofligandbindingandshowhowasimple
procedurecaninexpensivelyandaccuratelyeliminateit.
JournalofPhysicalChemB111:2242,2007 DOI
·
MobleyDL,DumontE,ChoderaJD,BaylyCI,CooperMD,andDillKA
Comparisonofchargemodelsforfixed-chargeforcefields:Small-moleculehydrationfree
energiesinexplicitsolvent
Wecompareanumberofpopularmethodsforderivingchargemodelsforsmallmolecules,derivinglessonsaboutbestpracticesfor
accuratesimulations.
JOHND.CHODERA-SLOANKETTERINGINSTITUTE-7
JournalofMolecularBiology371:1118,2007 DOI
·
MobleyDL,GravesAP,ChoderaJD,McReynoldsAC,ShoichetBK,andDillKA
Predictingabsoluteligandbindingfreeenergiestoasimplemodelsite
Weshowhowalchemicalfreeenergycalculationsarecapableofaccurateblindpredictionofsmall-moleculebindingaffinitiestoasimple
modelproteinbindingsite.
JournalofChemicalandTheoreticalComputation3:1231,2007 DOI
·
MobleyDL,ChoderaJD,andDillKA
Confine-and-releasemethod:Obtainingcorrectbindingfreeenergiesinthepresenceofprotein
conformationalchange
Wepresentageneralschemeforobtainingcorrectligandbindingaffinitieswhenproteinconformationalchangeisimplicatedinligand
binding.
JournalofChemicalPhysics126:155101,2007 DOI
·
ChoderaJD*,SinghalN*,SwopeWC,PiteraJW,PandeVS,andDillKA
AutomaticdiscoveryofmetastablestatesfortheconstructionofMarkovmodelsof
macromolecularconformationaldynamics
Proposingoneofthefirstautomatedalgorithmsfordiscoveringkineticallymetastablestatesofbiomoleculesfrommolecularsimulations,
thispapershowshowmanybiomoleculescanpossessnumerousdistinctlong-livedconformationalstateseventhoughthetheequilibrium
populationsofthesestatesmaytoosmallforstandardstructuralbiologytechniquestodetect.
ProceedingsoftheNationalAcademyofSciences104:11987,2007 DOI
·
OzkanSB,WuGA,ChoderaJD,andDillKA
ProteinFoldingbyZippingandAssembly
Areviewoftheutilityoftheproposedzippingandassemblymechanismfortheconcomitantformationofsecondaryandtertiary
structureinproteinfoldingforpredictingfoldingpathwaysandnativestructures.
JournalofChemicalTheoryandComputation3:26,2007 DOI
·
ChoderaJD,W.C.Swope,J.W.Pitera,C.Seok,andK.A.Dill
Useoftheweightedhistogramanalysismethodfortheanalysisofsimulatedandparallel
temperingsimulations
Theweightedhistogramanalysismethod(WHAM),amainstayofmoleculardynamicssimulationanalysis,isthoroughlyexplainedand
modernizedfortheanalysisofsimulatedandparalleltemperingsimulationdata.
JournalofChemicalPhysics125:084902,2006 DOI
·
MobleyDL,ChoderaJD,andDillKA
Ontheuseoforientationalrestraintsandsymmetrycorrectionsinalchemicalfreeenergy
calculations
Weillustratehoworientationalrestraintscanbeusedtogreatlyreducethecomputationaleffortinalchemicalcalculationsofligand
bindingfreeenergies,andclarifyhowsymmetrycorrectionsarenecessarywhenmoleculescontainsymmetricorpseudosymmetric
substituents.
MultiscaleModelingandSimulation5:1214,2006 DOI
·
ChoderaJD,SwopeWC,PiteraJW,andDillKA
Long-timeproteinfoldingdynamicsfromshort-timemoleculardynamicssimulations
Weshowhowthelong-timedynamicsofbiomolecularsystemscanberecapitulatedfromstatisticscollectedfromshortmolecular
simulationssamplingtransitionsbetweenkineticallymetastablestates.
JournalofComputationalChemistry24:89,2003 DOI
·
SeokC,RosenJB,ChoderaJD,DillKA
MOPED:Methodforoptimizingphysicalenergyparametersusingdecoys
Weproposeanewwaytooptimizeparametersforaphysicalenergyfunctionusingdecoystructuresforproteinfoldingstudies.
JournaloftheAmericanChemicalSociety123:12837,2001 DOI
·
LeeTS∗,ChongLT∗,ChoderaJD,andKollmanPA
Analternativeexplanationforthecatalyticproficiencyoforotidine5’-phosphatedecarboxylase
AcombinedQMandMDanalysisofpotentialplausiblemechanismstoexplaintheenormouscatalyticaccelerationofoneofthemost
proficientenzymesknown.
JOHND.CHODERA-SLOANKETTERINGINSTITUTE-8
ReviewsandCommentaries
CurrentOpinioninStructuralBiology25:135,2014 DOI
·
ChoderaJDandNoéF
Markovstatemodelsofbiomolecularconformationaldynamics
AreviewofexcitingrecentdevelopmentsinthestochasticmodelingofbiomoleculardynamicsusingtechniquesIoriginallyco-developed
tostudyproteinfolding.
AnnualReviewsinBiophysics42:121,2013 DOI
·
ChoderaJDandMobleyDL
Entropy-enthalpycompensation:Roleandramificationsforrationalliganddesign
Entropy-enthalpycompensationislikelyauniversalphenomena,butnotassevereaswidelythought,andirrelevantfordrugdiscovery
andliganddesign.
CurrentOpinioninStructuralBiology21:150,2011 DOI
·
ChoderaJD,MobleyDL,ShirtsMR,DixonRW,BransonKM,andPandeVS
Freeenergymethodsindrugdiscoveryanddesign:Progressandchallenges
Areviewofcurrentopportunitiesandchallengesforalchemicalfreeenergycalculationsindrugdiscoveryanddesign.
JournalofChemicalPhysics134:174105,2011 DOI
·
PrinzJH,WuH,SarichM,KellerB,FischbachM,HeldM,ChoderaJD,Schütte,andNoéF
Markovmodelsofmolecularkinetics:Generationandvalidation
CurrentbestpracticesforthegenerationandvalidationofMarkovstatemodelsfordescribingthestochasticdynamicsofbiomolecular
systems.
ProceedingsoftheNationalAcademyofSciences108:12969,2011 DOI
·
ChoderaJDandPandeVS
TheSocialNetwork(ofproteinconformations)
Anewmethodologyformappingproteinconformationalspacesisreminiscentofhowweusetwo-dimensionalmapstonavigatea
three-dimensionalworld.
AnnualReportsinComputationalChemistry3:41,2007 DOI
·
ShirtsMR,MobleyDL,ChoderaJD
Alchemicalfreeenergycalculations:Readyforprimetime?
Areviewofcurrentalchemicalfreeenergymethodologiesandtheirpotentialforuseindrugdiscoveryandliganddesign.
CurrentOpinioninStructuralBiology17(3):342,2007 DOI
·
DillKA,OzkanSB,WeiklTR,ChoderaJD,andVoelzVA
Theproteinfoldingproblem:Whenwillitbesolved?
Areviewofthecurrentstateoftheproteinfoldingproblem.
JOHND.CHODERA-SLOANKETTERINGINSTITUTE-9
Preprintsaheadofsubmission
Preprintaheadofsubmission bioRχiv
·
BoyceSE,TellinghuisenJT,andChoderaJD
Avoidingaccuracy-limitingpitfallsinthestudyofprotein-ligandinteractionswithisothermal
titrationcalorimetry
Wedemonstratehowtoavoidaccuracy-limitingproblemsinstandardisothermalcalorimetryexperimentsaswellascapturetheprimary
sourcesofuncertaintyinthermodynamicparameters.
Preprintaheadofsubmission arχiv
·
ChoderaJD,NoéF,HinrichsNS,KellerB,ElmsPJ,KaiserCM,Ewall-WiceA,MarquseeS,andBustamanteC
BayesianhiddenMarkovmodelanalysisofsingle-moleculebiophysicalexperiments
WepresentaBayesianhiddenMarkovmodelanalysisschemethatallowsbiomolecularconformationaldynamics—andthe
correspondinguncertaintyduetolimiteddata—tobeinferredfromsingle-moleculetrajectories.Thisapproachwasdevelopedfora
single-moleculestudyexaminingfoldingdynamicsofnascentproteinsexitingtheribosome[Science334:1723,2011·DOI].
Preprintaheadofsubmission arχiv
·
ChoderaJD,ElmsPJ,SwopeWC,PrinzJ-H,MarquseeS,BustamanteC,NoéF,andPandeVS
Arobustapproachtoestimatingratesfromtime-correlationfunctions
Wepresentasimple,robustapproachtoestimatingtwo-staterateconstantsfromexperimentalorsimulationdata.
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