Yog li dab tsi yog "protein folding"?

Tus kab mob COVID-19 tam sim no tau tsim ntau yam teeb meem uas cov neeg nyiag nkas tau zoo siab los tawm tsam. Los ntawm 3D luam tawm lub ntsej muag tiv thaiv thiab lub ntsej muag kho mob hauv tsev los hloov lub tshuab ua pa tag nrho, cov tswv yim ntws tau txais kev tshoov siab thiab lub siab sov. Nyob rau tib lub sijhawm, muaj kev sim ua kom nce mus rau lwm qhov chaw: hauv kev tshawb fawb txhawm rau tiv thaiv tus kabmob nws tus kheej.

Pom tau tias, lub peev xwm loj tshaj plaws rau kev txwv tsis pub muaj kev sib kis tam sim no thiab tshaj tawm tag nrho cov tom ntej yog nyob rau hauv txoj hauv kev uas sim mus rau hauv paus ntawm qhov teeb meem. Qhov "paub koj tus yeeb ncuab" txoj hauv kev no yog coj los ntawm Folding@Home xam qhov project. Ntau lab tus tib neeg tau kos npe rau qhov project thiab tau pub qee lub zog ua haujlwm ntawm lawv cov processors thiab GPUs, yog li tsim lub computer loj tshaj plaws hauv keeb kwm.

Tab sis dab tsi yog tag nrho cov exaflops siv rau? Yog vim li cas thiaj li yuav tsum tau pov xws li xam hwj chim ntawm protein folding? Dab tsi ntawm biochemistry ua haujlwm ntawm no, vim li cas cov protein yuav tsum tau quav txhua? Nov yog cov lus qhia ceev ceev ntawm cov protein folding: nws yog dab tsi, nws tshwm sim li cas, thiab vim li cas nws tseem ceeb.

Ua ntej, qhov tseem ceeb tshaj plaws: vim li cas thiaj xav tau cov protein?

Proteins yog cov qauv tseem ceeb. Lawv tsis tsuas yog muab cov khoom tsim rau cov hlwb, tab sis kuj tseem ua haujlwm ua enzyme catalysts rau yuav luag tag nrho cov tshuaj biochemical. Squirrels, ua lawv tus qauv los yog enzymatic, yog chains ntev amino acids, nyob rau hauv ib lub caij nyoog. Cov haujlwm ntawm cov protein yog txiav txim siab los ntawm cov amino acids nyob rau hauv qee qhov chaw ntawm cov protein. Yog hais tias, piv txwv li, ib qho protein yuav tsum tau khi rau qhov zoo molecule, qhov chaw khi yuav tsum tau ntim nrog cov amino acids tsis zoo.

Yuav kom nkag siab txog yuav ua li cas cov proteins tau txais cov qauv uas txiav txim siab lawv txoj haujlwm, peb yuav tsum mus dhau lub hauv paus ntawm molecular biology thiab cov ntaub ntawv ntws hauv lub cell.

Production, los yog kev qhia proteins pib nrog cov txheej txheem cov ntawv sau tseg. Thaum lub sij hawm transcription, DNA ob helix, uas muaj cov xov tooj ntawm tes cov ntaub ntawv genetic, ib nrab unwinds, tso cai rau cov nitrogen bases ntawm DNA los ua muaj rau ib tug enzyme hu ua. RNA polymerase. Txoj hauj lwm ntawm RNA polymerase yog ua ib daim ntawv theej RNA, lossis kev hloov pauv, ntawm cov noob. Daim ntawv no hu ua gene tub txib RNA (mRNA), yog ib qho molecule zoo tagnrho rau kev tswj cov khoom lag luam hauv cellular, cov ribosomesuas koom nrog ntau lawm, los yog tshaj tawm cov proteins.

Ribosomes ua zoo li cov tshuab sib dhos - lawv coj mRNA template thiab phim nws rau lwm yam me me ntawm RNA, hloov RNA (tRNA). Txhua tRNA muaj ob thaj chaw nquag - ib ntu ntawm peb lub hauv paus hu ua anticodon, uas yuav tsum phim cov codons sib xws ntawm mRNA, thiab ib qhov chaw rau khi ib qho amino acid tshwj xeeb rau qhov no codon. Thaum lub sij hawm txhais lus, tRNA molecules nyob rau hauv lub ribosome random sim khi rau mRNA siv anticodons. Yog tias ua tiav, tRNA molecule txuas nws cov amino acid rau yav dhau los, tsim qhov txuas txuas ntxiv hauv cov saw ntawm cov amino acids encoded los ntawm mRNA.

Qhov sib lawv liag ntawm cov amino acids no yog thawj theem ntawm cov protein structural hierarchy, uas yog vim li cas nws thiaj li hu ua thawj tus qauv. Tag nrho peb-dimensional qauv ntawm cov protein thiab nws cov haujlwm yog ncaj qha los ntawm cov qauv thawj, thiab nyob ntawm ntau yam khoom ntawm txhua tus ntawm cov amino acids thiab lawv cov kev sib cuam tshuam nrog ib leeg. Tsis muaj cov tshuaj lom neeg thiab cov amino acid cuam tshuam, polypeptides lawv yuav nyob twj ywm linear sequences tsis muaj peb-dimensional qauv. Qhov no tuaj yeem pom txhua zaus koj ua zaub mov - hauv cov txheej txheem no muaj thermal denaturation peb-dimensional qauv ntawm cov proteins.

Long-range bonds ntawm cov protein

Cov theem tom ntej ntawm cov qauv peb-seem, mus dhau qhov tseem ceeb, tau muab lub npe ntse theem nrab qauv. Nws suav nrog hydrogen bonds ntawm cov amino acids ntawm kev ua haujlwm ze. Lub ntsiab tseem ceeb ntawm kev ruaj ntseg kev sib cuam tshuam los ntawm ob yam: alpha helices и beta lis. Cov alpha helix tsim cov cheeb tsam nruj ntawm cov polypeptide, thaum daim ntawv beta tsim cov cheeb tsam du, dav. Ob qho kev tsim muaj ob qho tib si cov qauv thiab kev ua haujlwm, nyob ntawm cov yam ntxwv ntawm lawv cov amino acids. Piv txwv li, yog tias alpha helix feem ntau muaj hydrophilic amino acids, zoo li arginine tshuaj los yog lysine, ces nws yuav feem ntau yuav koom nrog cov tshuaj tiv thaiv aqueous.

Alpha helices thiab beta nplooj ntawv hauv cov protein. Hydrogen bonds tsim thaum lub sij hawm qhia protein.

Ob qho qauv no thiab lawv cov kev sib xyaw ua ke ua rau qib tom ntej ntawm cov qauv protein - tertiary qauv. Tsis zoo li cov tawg yooj yim ntawm cov qauv theem nrab, cov qauv tertiary feem ntau cuam tshuam los ntawm hydrophobicity. Cov chaw ntawm cov proteins feem ntau muaj hydrophobic amino acids, xws li alanine los yog methionine, thiab dej raug cais tawm ntawm qhov ntawd vim "greasy" xwm ntawm radicals. Cov qauv no feem ntau tshwm sim nyob rau hauv transmembrane proteins embedded nyob rau hauv lub lipid bilayer membrane nyob ib ncig ntawm lub hlwb. Cov cheeb tsam hydrophobic ntawm cov protein nyob twj ywm thermodynamically ruaj khov nyob rau hauv lub fatty ib feem ntawm daim nyias nyias, thaum lub hydrophilic cheeb tsam ntawm cov protein yog raug rau aqueous ib puag ncig ntawm ob sab.

Tsis tas li ntawd, kev ruaj ntseg ntawm cov qauv tertiary yog ua kom ntseeg tau los ntawm kev sib txuas ntev ntawm cov amino acids. Ib qho piv txwv classic ntawm xws li kev sib txuas yog disulfide choj, feem ntau tshwm sim ntawm ob cysteine ​​​​radicals. Yog tias koj hnov ​​​​tsw ib yam dab tsi zoo li cov qe lwj hauv cov plaub hau salon thaum lub sij hawm perm txheej txheem ntawm tus neeg mob cov plaub hau, ces qhov no yog ib feem denaturation ntawm lub tertiary qauv ntawm cov plaub hau keratin, uas tshwm sim los ntawm kev txo cov disulfide bonds nrog rau cov plaub hau. kev pab ntawm sulfur-muaj thiol sib tov.

Tertiary qauv yog ruaj khov los ntawm kev sib cuam tshuam ntev xws li hydrophobicity lossis disulfide bonds

Disulfide bonds tuaj yeem tshwm sim ntawm tshuaj cysteine radicals nyob rau hauv tib lub polypeptide saw, los yog ntawm cysteine ​​​​los ntawm txawv tiav chains. Kev sib cuam tshuam ntawm cov saw hlau sib txawv quaternary theem ntawm cov qauv protein. Ib qho piv txwv zoo ntawm quaternary qauv yog hemoglobin nws nyob hauv koj cov ntshav. Txhua lub hemoglobin molecule muaj plaub qhov zoo tib yam globins, cov protein ntau, txhua qhov uas muaj nyob rau hauv ib txoj hauj lwm tshwj xeeb hauv polypeptide los ntawm cov txuas hniav disulfide, thiab tseem cuam tshuam nrog heme molecule uas muaj hlau. Tag nrho plaub lub globins txuas nrog cov txuas txuas txuas nrog cov tshuaj disulfide, thiab tag nrho cov molecule khi rau ob peb lub pa molecules ib zaug, mus txog plaub, thiab muaj peev xwm tso tawm raws li qhov xav tau.

Cov qauv qauv hauv kev tshawb nrhiav kev kho mob

Polypeptide chains pib quav rau hauv lawv cov duab kawg thaum lub sij hawm kev txhais lus, raws li cov saw loj hlob tawm ntawm ribosome, zoo li ib daim ntawm lub cim xeeb-alloy hlau tuaj yeem ua rau cov duab nyuaj thaum cua sov. Txawm li cas los xij, raws li ib txwm nyob hauv biology, yam tsis yooj yim li ntawd.

Hauv ntau lub hlwb, cov noob tau sau tseg tau dhau los kho ntau yam ua ntej kev txhais lus, hloov pauv cov qauv ntawm cov protein ntau piv rau cov qauv ntshiab ntawm cov noob. Nyob rau hauv cov ntaub ntawv no, translational mechanisms feem ntau enlist kev pab ntawm molecular chaperones, cov proteins uas ib ntus khi rau nascent polypeptide saw thiab tiv thaiv nws los ntawm kev noj nyob rau hauv ib tug nruab nrab daim ntawv, los ntawm uas lawv yuav tsis muaj peev xwm mus rau qhov kawg.

Qhov no yog txhua yam hais tias kev kwv yees qhov kawg ntawm cov protein tsis yog ib txoj haujlwm tseem ceeb. Tau ntau xyoo lawm, tib txoj hauv kev los kawm cov qauv ntawm cov protein yog los ntawm kev siv lub cev xws li X-ray crystallography. Nws tsis yog txog thaum xyoo 1960s uas biophysical chemists pib tsim cov qauv kev suav ntawm cov protein folding, feem ntau tsom rau cov qauv tsim qauv thib ob. Cov txheej txheem no thiab lawv cov xeeb leej xeeb ntxwv yuav tsum muaj ntau cov ntaub ntawv tawm tswv yim ntxiv rau cov qauv tseem ceeb - piv txwv li, cov ntxhuav ntawm cov amino acid daim ntawv cog lus, cov npe ntawm hydrophobicity, them lub xeev, thiab txawm tias kev txuag ntawm cov qauv thiab kev ua haujlwm dhau lub sij hawm hloov pauv - tag nrho cov nyob rau hauv thiaj li yuav. kwv yees dab tsi yuav tshwm sim zoo li cov protein kawg.

Niaj hnub no cov txheej txheem suav rau kev kwv yees tus qauv theem nrab, xws li cov uas khiav ntawm Folding@Home network, ua haujlwm nrog kwv yees li 80% qhov tseeb-uas yog qhov zoo nkauj xav txog qhov nyuaj ntawm qhov teeb meem. Cov ntaub ntawv tsim los ntawm cov qauv kev kwv yees ntawm cov protein xws li SARS-CoV-2 spike protein yuav muab piv nrog cov ntaub ntawv los ntawm kev tshawb fawb lub cev ntawm tus kab mob. Raws li qhov tshwm sim, nws yuav ua tau kom tau txais cov qauv tseeb ntawm cov protein thiab, tej zaum, nkag siab tias tus kab mob txuas mus rau receptors li cas. angiotensin converting enzyme 2 ib tug neeg nyob rau hauv lub pa ib ntsuj av tau coj mus rau hauv lub cev. Yog tias peb tuaj yeem txheeb xyuas cov qauv no, peb yuav tuaj yeem nrhiav cov tshuaj uas thaiv kev khi thiab tiv thaiv kab mob.

Protein folding kev tshawb fawb yog lub hauv paus ntawm peb txoj kev nkag siab txog ntau yam kab mob thiab kab mob uas txawm tias thaum peb siv Folding@Home network los txiav txim seb yuav ua li cas kov yeej COVID-19, uas peb tau pom tawg hauv kev loj hlob tsis ntev los no, lub network yeej ' ua haujlwm ntev. Nws yog cov cuab yeej tshawb fawb uas tsim nyog rau kev kawm cov qauv protein uas ua rau muaj ntau ntau cov kab mob tsis zoo, xws li Alzheimer's disease lossis kab mob Creutzfeldt-Jakob, feem ntau tsis raug hu ua kab mob nyuj vwm. Thiab thaum lwm tus kab mob inevitably tshwm sim, peb yuav npaj pib tawm tsam nws dua.

Tau qhov twg los: www.hab.com