Umqedazwe wamanje we-COVID-19 udale izinkinga eziningi izigebengu eziye zajabulela ukuzihlasela. Kusukela ezivikelweni zobuso eziphrintiwe ze-3D kanye nemaski ezokwelapha enziwe ekhaya ukuze esikhundleni se-ventilator eyimishini egcwele, ukugeleza kwemibono bekugqugquzela futhi kufudumala inhliziyo. Ngesikhathi esifanayo, kube nemizamo yokuqhubekela phambili kwenye indawo: ocwaningweni oluhloselwe ukulwa negciwane ngokwalo.
Ngokusobala, amandla amakhulu okunqanda ubhubhane olukhona manje futhi adlule kuzo zonke ezilandelayo asendleleni ezama ukuthola umnyombo wenkinga. Le ndlela yokuthi “sazi isitha sakho” ithathwe iphrojekthi yekhompyutha ye-Folding@Home. Izigidi zabantu zibhalisele iphrojekthi futhi zinikela ngamanye amandla okucubungula amaphrosesa azo nama-GPU, ngaleyo ndlela zidale ikhompuyutha enkulu kunazo zonke [esabalalisiwe] emlandweni.
Kodwa wonke lawa ma-exaflops asetshenziselwa ini? Kungani kudingekile ukuphonsa amandla anjalo e-computing at ? Hlobo luni lwe-biochemistry olusebenzayo lapha, kungani amaprotheni edinga ukugoqa nhlobo? Nakhu ukubuka konke okusheshayo kokugoqa amaprotheni: ukuthi kuyini, kwenzeka kanjani, nokuthi kungani kubalulekile.
Okokuqala, into ebaluleke kakhulu: kungani amaprotheni adingekayo?
Amaprotheni ayizakhiwo ezibalulekile. Abahlinzeki nje ngezinto zokwakha zamaseli, kodwa futhi basebenza njengama-enzyme catalysts cishe kukho konke ukusabela kwe-biochemical. Izingwejeje, makube njalo noma , amaketango amade , etholakala ngokulandelana okuthile. Imisebenzi yamaprotheni inqunywa ukuthi yiziphi ama-amino acid atholakala ezindaweni ezithile kuphrotheni. Uma, ngokwesibonelo, iphrotheni idinga ukubophezela ku-molecule ene-positive charge, indawo ebophayo kufanele igcwaliswe ngama-amino acid anecala elibi.
Ukuze siqonde ukuthi amaprotheni athola kanjani ukwakheka okunquma umsebenzi wawo, kudingeka sihlole izisekelo zebhayoloji yamangqamuzana nokugeleza kolwazi kungqamuzana.
Ukukhiqiza, noma amaprotheni aqala ngenqubo . Ngesikhathi sokuloba, i-DNA double helix, equkethe ulwazi lofuzo lweseli, iyakhululeka kancane, ivumele izisekelo ze-nitrogen ze-DNA ukuthi zitholakale ku-enzyme ebizwa ngokuthi. . Umsebenzi we-RNA polymerase uwukwenza ikhophi ye-RNA, noma okulotshiweyo, kofuzo. Le khophi yofuzo olubizwa (mRNA), iyi-molecule eyodwa elungele ukulawula izimboni zamaprotheni ezingaphakathi kweseli, abenza umsebenzi wokukhiqiza, noma amaprotheni.
Ama-Ribosomes enza njengemishini yokuhlanganisa - athatha ithempulethi ye-mRNA futhi ayifanise nezinye izingcezu ezincane ze-RNA, (i-tRNA). I-tRNA ngayinye inezifunda ezimbili ezisebenzayo - ingxenye yezisekelo ezintathu ezibizwa , okumele ifane namakhodoni ahambisanayo e-mRNA, kanye nesiza sokubopha i-amino acid eqondene nalokhu. . Ngesikhathi sokuhumusha, ama-molecule e-tRNA ku-ribosome azama ngokungahleliwe ukubopha ku-mRNA esebenzisa ama-anticodon. Uma kuphumelele, i-molecule ye-tRNA inamathisela i-amino acid yayo kwedlule, yenze isixhumanisi esilandelayo ochungechungeni lwama-amino acid abhalwe ngekhodi i-mRNA.
Lokhu kulandelana kwama-amino acid yizinga lokuqala lesigaba samaprotheni sesakhiwo, yingakho kubizwa ngokuthi. . Isakhiwo sonke esinezinhlangothi ezintathu seprotheni kanye nemisebenzi yayo itholakala ngokuqondile esakhiweni esiyinhloko, futhi incike ezintweni ezihlukahlukene ze-amino acid ngayinye kanye nokusebenzisana kwazo. Ngaphandle kwalezi zakhiwo zamakhemikhali kanye nokusebenzisana kwe-amino acid, zizohlala zilandelana ngomugqa ngaphandle kwesakhiwo esinezinhlangothi ezintathu. Lokhu kungabonakala njalo uma upheka ukudla - kule nqubo kukhona okushisayo isakhiwo samaprotheni-ntathu.
Izibopho ezinde zezingxenye zamaprotheni
Izinga elilandelayo lesakhiwo esinezinhlangothi ezintathu, esidlula esokuqala, sanikezwa igama elihlakaniphile . Kuhlanganisa izibopho ze-hydrogen phakathi kwama-amino acid esenzo esiseduze. Ingqikithi eyinhloko yalokhu kusebenzisana okuzinzisa yehlela ezintweni ezimbili: и . I-alpha helix yakha isifunda esibophene ngokuqinile se-polypeptide, kuyilapho ishidi le-beta lakha isifunda esibushelelezi, esibanzi. Zombili lezi zakhiwo zinezakhiwo zombili zesakhiwo kanye nokusebenza, kuye ngezici zama-amino acid azo. Isibonelo, uma i-alpha helix iqukethe ikakhulukazi i-hydrophilic amino acid, njenge noma , khona-ke cishe izobamba iqhaza ekuphenduleni kwamanzi.
Ama-alpha helices namashidi e-beta kumaprotheni. Amabhondi e-Hydrogen ngesikhathi sokubonakaliswa kwamaprotheni.
Lezi zakhiwo ezimbili nezinhlanganisela zazo zakha izinga elilandelayo lesakhiwo samaprotheni - . Ngokungafani nezingcezu ezilula zesakhiwo sesibili, isakhiwo semfundo ephakeme sithonywa kakhulu yi-hydrophobicity. Izikhungo zamaprotheni amaningi ziqukethe kakhulu i-hydrophobic amino acid, njenge noma , futhi amanzi awafakwa lapho ngenxa yemvelo "enamafutha" yama-radicals. Lezi zakhiwo zivame ukuvela kumaprotheni e-transmembrane ashumekwe kulwelwesi lwe-lipid bilayer ezungeze amaseli. Izifunda ze-hydrophobic zamaprotheni zihlala zizinzile ngokwe-thermodynamically ngaphakathi kwengxenye enamafutha ye-membrane, kuyilapho izifunda ze-hydrophilic zamaprotheni zivezwe endaweni enamanzi nhlangothi zombili.
Futhi, ukuzinza kwezakhiwo zemfundo ephakeme kuqinisekiswa izibopho ezinde phakathi kwama-amino acid. Isibonelo sakudala sokuxhumana okunjalo , evame ukwenzeka phakathi kwama-cysteine radicals amabili. Uma uhogela okuthile okufana namaqanda abolile esaluni yezinwele ngesikhathi senqubo ye-perm ezinweleni zeklayenti, khona-ke lokhu bekuwukubonakaliswa okuyingxenye kwesakhiwo se-keratin equkethwe ezinweleni, okwenzeka ngokuncipha kwezibopho ze-disulfide nge usizo lwesulfure-equkethe izingxube.
Isakhiwo semfundo ephakeme sizinziswa ukusebenzisana okude okufana ne-hydrophobicity noma i-disulfide bond
Izibopho ze-Disulfide zingenzeka phakathi ama-radicals ochungechungeni olufanayo lwe-polypeptide, noma phakathi kwama-cysteine amaketanga aphelele ahlukene. Ukusebenzelana phakathi kwamaketanga ahlukene kwakha izinga lesakhiwo samaprotheni. Isibonelo esihle kakhulu se-quaternary structure kusegazini lakho. Ingqamuzana ngalinye le-hemoglobin linama-globin amane afanayo, izingxenye zamaprotheni, ngalinye eligcinwe endaweni ethile ngaphakathi kwe-polypeptide ngamabhuloho e-disulfide, futhi lihlotshaniswa ne-molecule ye-heme equkethe insimbi. Wonke ama-globin amane axhunywe amabhuloho e-intermolecular disulfide, futhi yonke i-molecule ibophezela kuma-molecule omoya amaningana ngesikhathi esisodwa, kuze kube kwamane, futhi iyakwazi ukuwakhulula njengoba kudingeka.
Ukumodela izakhiwo kufunwa ikhambi lezifo
Amaketango e-polypeptide aqala ukugoqa abe sesimweni sawo sokugcina ngesikhathi sokuhumusha, njengoba iketango elikhulayo liphuma ku-ribosome, kufana nocezu lwe-memory-alloy wire lungathatha izimo eziyinkimbinkimbi lapho kushisa. Kodwa-ke, njengenjwayelo ku-biology, izinto azilula kangako.
Kumaseli amaningi, izakhi zofuzo ezilotshiwe zihlelwa kabanzi ngaphambi kokuhumusha, okushintsha kakhulu ukwakheka okuyisisekelo kwephrotheni uma kuqhathaniswa nokulandelana kwesisekelo esimsulwa sofuzo. Kulokhu, izindlela zokuhumusha zivame ukucela usizo lwama-chaperones amangqamuzana, amaprotheni abopha okwesikhashana ochungechungeni lwe-polypeptide esanda kuzalwa futhi aluvimbele ukuthi luthathe noma yiliphi ifomu eliphakathi, lapho angeke akwazi ukudlulela kwelokugcina.
Konke lokhu kusho ukuthi ukubikezela ukuma kokugcina kweprotheni akuwona umsebenzi omncane. Emashumini eminyaka, okuwukuphela kwendlela yokufunda ukwakheka kwamaprotheni kwakuwukusebenzisa izindlela ezingokomzimba ezifana ne-X-ray crystallography. Kwaze kwaba ngasekupheleni kwawo-1960 lapho osokhemisi be-biophysical baqala khona ukwakha amamodeli wekhompyutha wokugoqa amaprotheni, ngokuyinhloko agxile ekubumbeni kwesakhiwo sesibili. Lezi zindlela kanye nenzalo yazo zidinga inani elikhulu ledatha yokufaka ngaphezu kwesakhiwo esiyinhloko - isibonelo, amathebula ama-engeli ebhondi ye-amino acid, izinhlu ze-hydrophobicity, izifunda ezikhokhisiwe, ngisho nokongiwa kwesakhiwo nokusebenza ngezilinganiso zezikhathi zokuziphendukela kwemvelo - konke ukuze qagela ukuthi kuzokwenzekani kubukeke njengeprotheni yokugcina.
Izindlela zanamuhla zokubala zokubikezela isakhiwo sesibili, njengalezo ezisebenza kunethiwekhi ye-Folding@Home, zisebenza cishe ngokunemba okungu-80%—okuhle kakhulu uma kucatshangelwa ubunkimbinkimbi benkinga. Idatha ekhiqizwe amamodeli aqagelayo kumaprotheni anjenge-SARS-CoV-2 spike protein izoqhathaniswa nedatha evela ezifundweni zomzimba zaleli gciwane. Ngenxa yalokho, kuzokwazi ukuthola ukwakheka okuqondile kwephrotheni futhi, mhlawumbe, ukuqonda ukuthi igciwane linamathela kanjani kuma-receptors. umuntu otholakala emgudwini wokuphefumula oholela emzimbeni. Uma singakwazi ukuthola lesi sakhiwo, singakwazi ukuthola izidakamizwa ezivimba ukubopha nokuvimbela ukutheleleka.
Ucwaningo lokugoqa amaprotheni luwumgogodla wokuqonda kwethu izifo eziningi nezifo kangangokuthi noma sisebenzisa inethiwekhi ye-Folding@Home ukuthola ukuthi singayinqoba kanjani i-COVID-19, esiyibone iqhuma ekukhuleni kamuva nje, inethiwekhi ngeke' ngingenzi lutho isikhathi eside. Iyithuluzi lokucwaninga elikufanelekela kahle ukutadisha amaphethini amaprotheni abangela inqwaba yezifo zokungasoleki kahle kwamaprotheni, njengesifo i-Alzheimer's noma isifo se-Creutzfeldt-Jakob, esivame ukubizwa ngokungeyikho ngokuthi isifo senkomo esihlanyayo. Futhi lapho elinye igciwane livela nakanjani, sizobe sesilungele ukuqala ukulwa nalo futhi.
Source: www.habr.com