3P-055 Modeling allosteric conformational changes of different proteins with chameleon Go Model(Protein:Property,The 47th Annual Meeting of the Biophysical Society of Japan)
3P-055 異なる蛋白質のアロステリックな構造変化のカメレオン郷モデルによるモデリング(蛋白質-物性(安定性,折れたたみなど),第47回日本生物物理学会年会)

Syogo Yokota, Takahiro Yamashita, Tomoki Terada
2009 Seibutsu Butsuri  
TheBiophysicalSociety of Japan General IncorporatedAssociation 3P053 Eeec7MX7U-Ozaafh\ StatistacalMechamcalTheoryofPreteinAllostcry Kdzllhito ltoh (1) Masdki Sdsdl (1} (rl) Depai tfnenp oj Anptied Ph}sics Ningoya V}i-ersiij) Allogtenc change of protein conformataon is esgentanl for many biological regulator} procesgeg The mechamsm of allostry however gta11 remaing elusive Expenmelltal results have shown that a protem can take multiple conformatiolls in the native state and that the allosteric
more » ... at the allosteric chdinge is a shift in population of those LonformatLons mduLed by bmdmg oHigand or other etfectoi mDleLule to the prutein An important gtcp to elucidate the rnechanigrn ol guch population ghilt ig to analyze the quantatatave free energy surface oNer multaple native conformataons and henLe it Lb btrongly dcbiTLd to devL]ep a statistieal mLLhamLal theDry to descr]bc LhL allogteTic transition by calculating the tree energy gurtace We propose a statastical mechanical medel of allebtery to address this issue which is an extenbion of the btruLtarL based modcl o[ protc]n fo]ding to cases of multiple nit]ve conlomiations Partmon functaon is calculated exactly within the model and the free energy surface of allotstery is denved We report the results obtdlned by app!ymg the model to some exarnple proteins Cooperativity and fluctuations m the allobterLL trdnsition are digLusgLd The modLl ghows that thL free energy barner ot the trangition ig lowered by thc cnnopic mcchamsm m which thL entropy comlng fi oin thc combinatorial nurnbeT of configurations of mixcd activL and inactive local conformataons 3pOs4 asfi7).tr),7JV,leMoktsas"-ofiR EhtwfimaoMZ Molecular dynamics study of temperature and prebsuTe effects on a biomo]eLule with genera]]Led ensemb]e algunthms GLnLralizcdcngemble algonthrns have been wide!y used tor simulationg ot pToteins and peptudes Although many simulataons with generakzed ensemble algomthms have been perfoimed m the Lanonical ensemble a censtant tempelriture md presgure method should be Lmployed when physical quantit]eg for an igobanc isothermal engemble arc to be obtained High pieggllre denaturation of proteing ig guch an example In the pTesent study we performed molecular dynaJnics sirnulations of a sygtem of an alanine dipeptade m explicit water molecutes We used a few generahzed ensemble algonthms whiLh are all tvvo dLrmensional extensionb of the origmal one dimensional mLthodg Narnely randorn walkg ]n tcrnpcraturL and prcsgurL gpace are realized We calculated physical quantataes at several tempeTature ancl prcsbuLe values and coinpared the regu]Ls atnong lhe empJeyed geneialvcd cnscmb]ca]gonthrng I"s found that the each bimulation can sample phyvcal quantaueb etfectively and that the LernpcTaLure and piessuTe dependence oi the a]anme dipLptide systcrn aTe well represented We show that thetse generahzed entsemble algonthms for isobariL isotherma] s]mulatTons aTe vLry useful for studying temperature and pressure effects on protelns #ts6EeMo7mxrUybzaasmsQ{tohptvt>eeB{fjv [:at6E7"Utzot Modeling allosteric contormational chemiges ot drtterent protems with chameleon Go Model (1) TakdhiTo Yamdshitd (1) Tomoki Terdrid {2) C") Department of S"ence and Lnstneentng Nage)a UntvLrsay (2J DLpaitmLnt of appli"l A simulated anneahng molecular dyndmiLb simulataon with a genetaccrossoverforprotemsystems Yeshrtakc Sakac (1) lomoyuki El]roydsu (2) MitsunerL Miki (3) Yuke OkameLo (1) (rl) Department ef Phvstcs IVagexa Univasitv f2) Depamnent of BIoniedtcal Injbrmxltten Dohhibha Vmverhity r3) Department of lnteUtgem itiprmatten Envn"nns and S"ences Doshtsha tiniverstti) We propose a con]orniatLonal seaich method m order to fmd a rninLmum energy structure toi prote]n sygLerng In this method a simulated annealmg simulation is combined with a gcnetic eiogsover whiLh is one of the procedurcg ot genetie algorithm The simulated annealing is a poweTfu] method foi locat conformational searLh AddLtionally the gene"c algorithm can gearch thc global Lviiformational space Our mcthod mLurporates thebe attractave features In the prLvious works we have been usmg the Monte Carlo algonthm for s]mulated anneahng In the prLsLnt work we employ the rnolecular dynamics algoi]thm ]nstedd Moleculdr dynamics mcthod !g rnoie suitable for tocal conformational seareh than Monte Carlo sLheme and this is the mam motivatiom for LhL present work We performcd gcncLic LrogsoNer foi the conformations dunng thc gimulated annealmg molecular dynamics simu]ations Jn the Lrossover procedure pa"s ol different offsprmg are produced by recornbination of pdirs of parental conLormatlons landornly seleLted from all the confoTmations Atter that pairs of thc lowereneigy contormations ace selected frorn parental and otisprmg contorrnations In Lhis nicthod this LrDbbever proceduie is pertormed for cvery several simulated annealmg molecular dynamiLs stepts As the eontormational variables for the genetac crosgover wc used dihedral angles m the amino acid sequelce wLth some length randomly se!ected [n order to examne the ettects ot our nicthod we Lompared our results with those of thL norn]al simulited mnealmg molecular dynamics s]mulations and iephca exchange molLcular dynam]Ls bLmulations using two peptidLs namely C peptide and G peptade The results showed that the Lonformations which have IowLr Lnergy than those obtained fiom the other t" o meLhods vvere obtained 3P OS7 Ke]chi gugimoin (1) SchootofSttence Protem structures are very important to know their functaons membrane protein structares are diffiLult to detcrmme by experiments our TescaTeh is to predict membrane protem stnJctures by iiTst pnnuples Lomputer sirnulations from their arnmo acid sequLnce infomiation Our simulation method ]g repliea exchange Monte Carlo method and lip]d moleeules aie not taken mto account explicitly Instead we add gimpie funcuonb to potential energy vvhich rLprcsent membrame effetts approximately Ollr gimulabon has two steps First we piedict uansmembrane hehx regions from aminoacid sequcncL using a predictJon tool such as SOSUI We then pLrfbrm a replica exchange Monte Carlo s]mulation and determme global mmimum frLL energy btate To find the global minmium [ree cneigy gtate we use the pnncipal componLnt analysh Ab a first example we recreated succcggful]y the NMR tstructure of two trangmernbiane helixes of glycophonn A We prcscnt the details of these and othcr simu]ation reguLtg vVvhNdeE>rh)Lm-szv--i-igmvitmee>Ab fiOasfii,fi4-it=tz--]> PrLdiction of rnembrane protem structuies by rcpl]caex ¢ hange MonteCarlosimuJationb Hironeri Kekubo {2} Yuko Okameto (1) (tJ) Depa,tuent ot Phxsics Nago)a Umversi-f2) Deparnnent ot Chemtslr) Vntv"sirv ofHouston) However cgpL"ally The airn of 3P 055 Syogo Yokotd Compuk2tienal Ph)sics rVagoul Untversttv) Ligand mduced conformauonal changes of proteins may well be largely deteinn]ined by the topologv ol proteing girnilarly to pTotein tolding Therefore coarse grarned rnodelmg of protems can be helpfu1 in undeistandmg a design pllnupie for atomiL interaLtions in 1igand bLnding proteLnts We have previously reported that the free energy landscape obLamcd wilh a inodified Go 1ike model called chameleon Go model can explarn experimental findings about the Lenfoumataenal Lhangets of adeiiylate kmatse Chdmeteon Go model hag ]ocal interaetiong with gingle eneTgy rmn]ma -hiLh can move accordrng to the changes m local surroundmgs This is in sharp contrast with thc several preLedmg modTfiLations of Go 1]ke model with double energy mimma Despite of this difference chameleon Go model can describe two gtatc LDntormational changes of adenylate kinase We alsD found thdt the opell state of adenylate kinase can be stabilized by entropy not by energy "hereas the closed state Lan be btabiliicd 1)y energtr We here apply this model to several protems other than adenylate krnase WL obhin fiee energy ldndbcdpes foi thei; conformational changes to assess the geneidtity of the dboye findillgb Besides we ask whether the diversity of Iigand bindmg mechamsms can be captured by applying i smg]L chan]clLon Go model to these proteins The weakenmg effect of the local mteiaction by loeal unfo]d]ng on the fi ee energy landsLape wt11 also be disLussed 3P056 SMe9AMeMVke,""-enh\-S=tr--y 3P 058 NnofumiRJKFAD xxth-"+geut,feMtik7 1-P.r F BglasOneut Amyloid beta oligomer fonnation btudied by newly developcd smglemoleculcana]yysmethod Tcrada U} Tamotbu 7al.e {l) Masafunll Sakono (1) Mvuo Macda (1) ((1) Am} loid beta (Ab) is 4 kDa peptide which is thought te form aggiegaLes such ds ohgorncrs and hbm]s ind to cauge Alzheimer chsLigL (AD) Recently it has been suggested thaL soluble Ab ohgvmers are the Lausativc agent of AD since suLh ohgorners are more cytotoxic than tibnls It was aitse suggested that 4b ollgomerts afftLt not only cell death but also eaily stage of Lell dysfunctien and eause memoTy losg However, the mechanism ho" golublL ehs.omers are produced s sti]1 u"known In thig stady we analyzed Ab ohgomer distnbutien m vitro at smgle molccule Ievel usmg photon counting histogranl (PCH)(Terada N et a] (2007) Biophys J 92 2162) and tota] mternal refiection fluorLgcLnLe m]Lroscopy (TIRFM) Usmg TIRFM fiuorescLnt intensity of monomer is obtained from drscrete photobtedchimg Using PCH method thL number of protomers m ohgomers apd Loncentrations are obtained tTom hhtograms of photons from fiuorescent molcculLs diffugmg through the confocal volume Fibmls of FITC labclcd Ab were prepared and Lhcy were sonicated to rnake oligomers Ohgomenzntaon wag Lonfirmed by TIRFM WL obse-ed somcated t]bnls by PCH dnd found oligomers sucLLssful]y lt was shown Uiat PCH is usefu1 to analyLc Ab o]]gomer
doi:10.2142/biophys.49.s160_3 fatcat:6754omq2hrfbfayiimho5aelxi