Ke yintoni kanye kanye “ukusonga iprotein”?

Ubhubhani wangoku we-COVID-19 udale iingxaki ezininzi abathi abaqweqwedisi bonwabele ukuhlasela. Ukusuka kwi-3D eprintiweyo izikhuselo zobuso kunye neemaski zonyango ezenziwe ekhaya ukuya endaweni ye-ventilator egcweleyo yoomatshini, ukuhamba kwezimvo kwakukhuthaza kwaye kufudumeza intliziyo. Ngelo xesha, kwakukho iinzame zokuqhubela phambili kwenye indawo: kuphando olujoliswe ukulwa nentsholongwane ngokwayo.

Kuyabonakala ukuba, awona mandla anamandla okumisa ubhubhane wangoku kunye nokugqithisa zonke ezi zilandelayo zilele kwindlela ezama ukufikelela kweyona ngcambu yengxaki. Le ndlela "yazi utshaba lwakho" ithathwa yiprojekthi yekhompyuter yeFolding@Home. Izigidi zabantu zibhalisele iprojekthi kwaye zinikela ngamanye amandla okusebenza eprosesa zabo kunye neeGPU, ngaloo ndlela zenza eyona [esasazwe] enkulu kwikhompyuter kwimbali.

Kodwa zonke ezi exflops zisetyenziselwa ntoni? Kutheni kuyimfuneko ukuphosa amandla anjalo ekhompyutheni ukusonga iprotheni? Loluphi uhlobo lwebhayoloji esebenzayo apha, kutheni iiproteni zifuna ukusonga konke? Nantsi inkcazo ekhawulezayo yokusonga iprotein: yintoni, yenzeka njani, kwaye kutheni ibalulekile.

Okokuqala, eyona nto ibalulekileyo: kutheni kufuneka iiprotheni?

Iiprotheyini zizakhiwo ezibalulekileyo. Ababoneleli nje ngezinto zokwakha kwiiseli, kodwa bakwasebenza njenge-enzyme catalysts phantse zonke iimpendulo ze-biochemical. Oomatse, makube njalo ulwakhiwo okanye i-enzymatic, ngamatyathanga amade amino acid, ibekwe kulandelelwano oluthile. Imisebenzi yeeprotheyini imiselwa ukuba i-amino acids ibekwe kwiindawo ezithile kwiprotheni. Ukuba, umzekelo, iprotheni idinga ukubopha kwi-molecule ehlawulisiweyo, indawo yokubopha kufuneka izaliswe ngama-amino acids ahlawulwe kakubi.

Ukuqonda indlela iiprotheyini ezisifumana ngayo isakhelo esimisela umsebenzi wazo, kufuneka sidlule kwiziseko zebhayoloji yemolekyuli kunye nokuhamba kolwazi kwiseli.

Imveliso, okanye intetho iiprotheni ziqala ngenkqubo imibhalo ekhutshelweyo. Ngexesha loshicilelo, i-DNA double helix, equlethe ulwazi lwemfuza yeseli, ikhulula ngokuyinxenye, ivumela iziseko ze-nitrogen ze-DNA ukuba zifumaneke kwi-enzyme ebizwa ngokuba. I-RNA polymerase. Umsebenzi weRNA polymerase kukwenza ikopi yeRNA, okanye ushicilelo lwemfuza. Le ikopi yemfuza ebizwa isithunywa RNA (mRNA), yimolekyuli enye efanelekileyo yokulawula iifektri zeprotheyini ze-intracellular, iiribosomesababandakanyeka kwimveliso, okanye usasazo iiprotheni.

IiRibosomes zisebenza njengoomatshini bokuhlanganisa - bathatha ithemplate ye-mRNA kwaye bayitshatise namanye amaqhekeza amancinci e-RNA, ugqithiselo lwe-RNA (tRNA). I-tRNA nganye inemimandla emibini esebenzayo - icandelo leziseko ezintathu ezibizwa i-anticodon, ekufuneka ithelekise iikhodons ezihambelanayo ze-mRNA, kunye nesiza sokubopha i-amino acid elungiselelwe oku. ikhodon. Ngexesha loguqulelo, iimolekyuli ze-tRNA ezikwiribosome zizama ngokungakhethiyo ukubophelela kwi-mRNA zisebenzisa ii-anticodons. Ukuba iphumelele, imolekyuli ye-tRNA incamathisela i-amino acid yayo kweyangaphambili, yenze ikhonkco elilandelayo kumxokelelwano wee-amino acid ezifakwe ngekhowudi yi-mRNA.

Olu landelelwano lwee-amino acids linqanaba lokuqala loluhlu lweprotheyini yesakhiwo, yiyo loo nto ibizwa ngokuba isakhiwo sokuqala. Isakhiwo esipheleleyo se-dimensional ye-protein kunye nemisebenzi yayo iphuma ngokuthe ngqo kwisakhiwo sokuqala, kwaye ixhomekeke kwiimpawu ezahlukeneyo ze-amino acids kunye nokusebenzisana kwazo. Ngaphandle kwezi zakhiwo zeekhemikhali kunye nokusebenzisana kwe-amino acid, iipolypeptides ziya kuhlala zilandelelana ngaphandle kolwakhiwo olunemigangatho emithathu. Oku kunokubonwa rhoqo xa upheka ukutya - kule nkqubo kukho i-thermal idenaturation Ulwakhiwo olunemigangatho emithathu yeeprotheni.

Iibhondi ezide zeprotheyini

Inqanaba elilandelayo lesakhiwo esine-dimensional emithathu, ehamba ngaphaya kweyokuqala, yanikwa igama elihlakaniphile isakhiwo sesibini. Ibandakanya iibhondi ze-hydrogen phakathi kwee-amino acids zesenzo esisondeleyo. Undoqo ophambili wolu nxibelelwano luzinzisa wehla kwizinto ezimbini: ialpha helices и uluhlu lwe-beta. I-alpha helix yenza ummandla obambene ngokuqinileyo we-polypeptide, ngelixa i-beta sheet yenza ummandla ogudileyo, obanzi. Zombini iifom zinezakhiwo kunye nokusebenza, ngokuxhomekeke kwiimpawu ze-amino acids yazo. Ngokomzekelo, ukuba i-alpha helix iqulethe ubukhulu becala i-hydrophilic amino acids, njenge arginine okanye ilysine, ngoko ke kuya kuba nenxaxheba kakhulu ekuphenduleni kwamanzi.

I-alpha helices kunye namaphepha e-beta kwiiprotheni. Iibhondi zeHydrogen ngexesha lokubonakaliswa kweprotheyini.

Ezi zakhiwo zimbini kunye nokudityaniswa kwazo zenza inqanaba elilandelayo leprotein - isakhiwo semfundo ephakamileyo. Ngokungafaniyo neziqwenga ezilula zesakhiwo sesibini, ulwakhiwo lwemfundo ephakamileyo luphenjelelwa ikakhulu yi-hydrophobicity. Amaziko amaninzi eeprotheyini aqulethe i-hydrophobic amino acids ephezulu, njenge ialanine okanye imethionine, kwaye amanzi akabandakanywanga apho ngenxa yendalo "enamafutha" yeeradicals. Ezi zakhiwo zihlala zivela kwiiprotheni ze-transmembrane ezifakwe kwi-lipid bilayer inwebu ejikeleze iiseli. Imimandla ye-hydrophobic yeeprotheni ihlala i-thermodynamically stable ngaphakathi kwi-fatty part of the membrane, ngelixa imimandla ye-hydrophilic yeprotheni ibonakaliswe kwindawo enamanzi kumacala omabini.

Kwakhona, ukuzinza kwezakhiwo eziphakamileyo kuqinisekiswa ngamabhondi omde phakathi kwe-amino acids. Umzekelo oqhelekileyo wonxibelelwano olunjalo ibhulorho ye-disulfide, ihlala isenzeka phakathi kwe-cysteine ​​​​radicals ezimbini. Ukuba uphunga into encinci njengamaqanda abolileyo kwi-salon yeenwele ngexesha lenkqubo ye-perm kwizinwele zomthengi, oku yayiyinxenye ye-denaturation yesakhiwo se-keratin equlethwe kwiinwele, eyenzeka ngokunciphisa amabhondi e-disulfide kunye neenwele. uncedo lwesulfure equlethe thiol imixube.

Ulwakhiwo lwenqanaba eliphezulu lizinziswe lunxibelelwano olude olufana ne-hydrophobicity okanye i-disulfide bond.

Iibhondi ze-disulfide zingenzeka phakathi cysteine radicals kwitsheyini ye-polypeptide efanayo, okanye phakathi kwama-cysteines asuka kumatyathanga ahlukeneyo apheleleyo. Ukusebenzisana phakathi kweendlela ezahlukeneyo zamakhonkco ikota umgangatho weprotheyini yesakhiwo. Umzekelo obalaseleyo wesakhiwo se-quaternary yi ihemoglobin kusegazini lakho. Imolekyuli nganye ye<em>hemoglobin ineeglobin ezine ezifanayo, iinxalenye zeprotini, nganye kuzo ikwindawo ethile kwipolypeptide ngeebhulorho zedisulfide, yaye ikwanxulunyaniswa nemolekyuli yeheme eneiron. Zonke iiglobin ezine ziqhagamshelwe ngeebhulorho ze-intermolecular disulfide, kwaye yonke imolekyuli ibophelela kwiimolekyuli zomoya ezininzi ngaxeshanye, ukuya kuthi ga kwezine, kwaye iyakwazi ukuzikhulula njengoko kufuneka.

Ukwenza imodeli yezakhiwo kukhangelwa unyango lwezifo

Amatyathanga ePolypeptide aqala ukugoqa abe kwimilo yawo yokugqibela ngexesha lokuguqulelwa, njengoko ikhonkco elikhulayo liphuma kwi-ribosome, kufana nje neqhekeza le-memory-alloy wire inokuthatha iimilo ezintsonkothileyo xa ishushu. Nangona kunjalo, njengesiqhelo kwibhayoloji, izinto azilula kangako.

Kwiiseli ezininzi, iijini ezikhutshelweyo zihlelwa ngokubanzi phambi kokuguqulelwa, ngokuphawulekayo ukutshintsha isiseko seprotein xa kuthelekiswa nolandelelwano olusulungekileyo lwejini. Kule meko, iindlela zokuguqulela zihlala zifuna uncedo lwee-molecular chaperones, iiprotheyini ezibophelela okwethutyana kwikhonkco le-polypeptide esakhulayo kwaye zithintele ukuba zithathe nayiphi na ifom ephakathi, apho abayi kukwazi ukuqhubela phambili ukuya ekugqibeleni.

Konke oku kuthetha ukuba ukuxela kwangaphambili imilo yokugqibela yeprotheni ayingomsebenzi omncinci. Kangangamashumi eminyaka, ekuphela kwendlela yokufunda ubume beeproteni yayingeendlela zomzimba ezifana neX-ray crystallography. Kwakungekho de kwasekupheleni kweminyaka yoo-1960 apho iikhemisti zebhayophysical zaqala ukwakha iimodeli zokudityaniswa kweprotein, ngokuyintloko zigxile kumzekelo wesibini. Ezi ndlela kunye nenzala yazo zifuna izixa ezikhulu zedatha yegalelo ukongeza kulwakhiwo oluphambili - umzekelo, iitafile ze-amino acid bond angles, uluhlu lwe-hydrophobicity, ilizwe elihlawulisiweyo, kunye nokugcinwa kwesakhiwo kunye nomsebenzi ngaphezu kwexesha lokuzivelela kwemvelo - konke ukuze qikelela ukuba kuya kwenzeka ntoni kujongeka njengeprotein yokugqibela.

Iindlela zanamhlanje zokubala zoqikelelo lwesakhiwo sesibini, ezifana nezo zisebenza kwi-Folding@Home network, zisebenza malunga ne-80% ngokuchanekileyo-nto leyo intle kakhulu xa kuqwalaselwa ubunzima bengxaki. Idatha eveliswe ziimodeli zokuqikelela kwiiproteni ezinje nge-SARS-CoV-2 spike protein iya kuthelekiswa nedatha evela kwizifundo zomzimba zentsholongwane. Ngenxa yoko, kuya kwenzeka ukuba ufumane isakhiwo esichanekileyo seprotheni kwaye, mhlawumbi, uqonde indlela intsholongwane enamathela ngayo kwi-receptors. I-angiotensin iguqula i-enzyme 2 umntu obekwe kwindlela yokuphefumla ekhokelela emzimbeni. Ukuba sinokufumanisa esi sakhiwo, sinokukwazi ukufumana amachiza athintela ukubopha kunye nokuthintela usulelo.

Uphando lokusonga iiprotheyini lusembindini wokuqonda kwethu izifo ezininzi kunye nosulelo kangangokuba naxa sisebenzisa inethiwekhi yeFolding@Home ukubona indlela yokoyisa i-COVID-19, esiyibone iqhuma ekukhuleni mva nje, inethiwekhi ayizukuphumelela. ndingasebenzi ixesha elide. Sisixhobo sophando esikufanelekelayo ukufunda ngeeproteni ezibangela intaphane yezifo ezinxulumene nokungalungelelani kweproteni, njengesifo sika-Alzheimer okanye isifo seCreutzfeldt-Jakob, esidla ngokubizwa ngokuphosakeleyo ngokuba sisifo semad cow. Kwaye xa enye intsholongwane ibonakala ngokungaphephekiyo, siya kuba sikulungele ukuqalisa ukulwa nayo kwakhona.

umthombo: www.habr.com