Saka chii chaizvo chinonzi "protein kupeta"?

Denda razvino reCCIDID-19 rakagadzira matambudziko mazhinji ayo matsotsi ave kufara kurwisa. Kubva ku3D yakadhindwa nhovo dzechiso uye masks emumba ekurapa kutsiva yakazara mechanic ventilator, kuyerera kwemazano kwaikurudzira uye kuchipisa moyo. Panguva imwecheteyo, pakanga paine kuedza kufambira mberi mune imwe nzvimbo: mukutsvaga kwakanangana nekurwisa hutachiona pachahwo.

Sezviri pachena, mukana mukuru wekumisa denda razvino uye kupfuura ese anotevera ari munzira inoedza kusvika pamudzi wedambudziko. Iyi "ziva muvengi wako" nzira inotorwa neFolding@Home komputa chirongwa. Mamirioni avanhu akasaina kuchirongwa ichi uye vari kupa rimwe resimba rekugadzirisa revagadziri vavo uye maGPU, nekudaro vachigadzira yakakura kwazvo [yakaparadzirwa] supercomputer munhoroondo.

Asi maexaflops ese aya anoshandiswa chii chaizvo? Sei zvakakosha kukanda simba rekombuta rakadaro kupeta mapuroteni? Imhando ipi yebiochemistry iri kushanda pano, nei mapuroteni achida kupeta zvachose? Heino mhedziso yekukurumidza yeprotein kupeta: chii, kuti zvinoitika sei, uye nei zvakakosha.

Kutanga, chinhu chinonyanya kukosha: nei mapuroteni achidiwa?

Mapuroteni zvimiro zvakakosha. Ivo havangopi chete zvekuvaka masero, asi zvakare anoshanda se enzyme catalysts kune anenge ese biochemical maitiro. Squirrels, ngave ivo structural kana enzymatic, iketani refu amino acids, iri mune imwe nhevedzano. Mabasa emapuroteni anotariswa neapi amino acids anowanikwa mune dzimwe nzvimbo paprotein. Kana, semuenzaniso, puroteni inoda kusungirira kune yakanaka chaji molecule, inosunga saiti inofanirwa kuzadzwa neamino acids inochajiswa zvisina kunaka.

Kuti tinzwisise kuti mapuroteni anowana sei chimiro chinotaridza basa rawo, isu tinofanirwa kuenda pamusoro pezvakakosha zvemolecular biology uye kuyerera kweruzivo muchitokisi.

Kugadzirwa, kana kutaura mapuroteni anotanga nekuita zvinyorwa. Panguva yekunyora, DNA double helix, iyo ine ruzivo rwemajini esero, inosunungura zvishoma, ichibvumira mabhesi enitrogen eDNA kuti awanikwe kune enzyme inonzi. RNA polymerase. Basa reRNA polymerase nderekugadzira RNA kopi, kana kunyora, yejini. Iyi kopi yejini yakadanwa mutumwa RNA (mRNA), imorekuru rimwe chete rakanakira kudzora intracellular protein mafekitori, ribosomesvari kuita basa rekugadzira, kana broadcast mapuroteni.

Ribosomes anoita semichina yekusangana - vanotora mRNA template voifananidza nezvimwe zvidiki zveRNA, chinjanisa RNA (tRNA). Imwe neimwe tRNA ine matunhu maviri anoshanda - chikamu chemabhesi matatu anonzi anticodon, iyo inofanirwa kuenderana nemakodoni emRNA, uye saiti yekusunga amino acid yakanangana neizvi. codon. Panguva yekushandura, mamorekuru etRNA ari muribosome anoedza kusunga kumRNA achishandisa maanticodon. Kana ikabudirira, iyo tRNA molecule inosungirira amino acid yayo kune yapfuura, ichigadzira chinongedzo chinotevera muketani yemaamino acids yakavharidzirwa nemRNA.

Uku kutevedzana kweamino acids ndiyo yekutanga nhanho yeprotein structural hierarchy, ndosaka ichinzi. chimiro chekutanga. Iyo yese-matatu-dimensional chimiro cheprotein uye mabasa ayo anotorwa zvakananga kubva kune yekutanga chimiro, uye zvinoenderana neakasiyana emhando yeimwe neimwe yeamino acid uye kudyidzana kwavo kune mumwe nemumwe. Pasina aya emakemikari zvivakwa uye amino acid kupindirana, polypeptides dzaizoramba dzakatevedzana dzisina mativi matatu-dimensional chimiro. Izvi zvinogona kuonekwa nguva dzose paunobika zvokudya - mune iyi nzira kune kupisa denaturation matatu-dimensional maitiro emapuroteni.

Kureba kwezvisungo zveprotini zvikamu

Chikamu chinotevera chetatu-dimensional chimiro, chichipfuura chepakutanga, chakapihwa zita rakangwara chimiro chechipiri. Inosanganisira hydrogen zvisungo pakati peamino acids zvechiito chiri pedyo. Chinhu chikuru chekudyidzana uku kudzikamisa chinodzika kune zvinhu zviviri: alpha helices и beta list. Iyo alpha helix inoumba dunhu rakasungwa zvakasimba repolypeptide, ukuwo beta pepa richiumba iyo yakatsetseka, yakafara dunhu. Maumbirwo ese ari maviri ane zvese zvimiro uye zvinoshanda zvimiro, zvinoenderana nehunhu hweanoumba amino acids. Semuenzaniso, kana iyo alpha helix inosanganisira zvakanyanya hydrophilic amino acids, senge arginine kana lysine, zvino zvinozonyanya kutora chikamu mukuita kwemvura.

Alpha helices uye beta mapepa mumapuroteni. Hydrogen bonds fomu panguva yeprotein expression.

Izvi zviviri zvimiro uye musanganiswa wavo zvinoumba inotevera nhanho yeprotein chimiro - chimiro chepamusoro. Kusiyana nezvidimbu zvakapusa zvechimiro chechipiri, chimiro chepamusoro chinonyanya kukanganiswa ne hydrophobicity. Nzvimbo dzemapuroteni mazhinji dzine yakanyanya hydrophobic amino acids, senge alanine kana methionine, uye mvura inobviswa kubva ipapo nekuda kwe "greasy" hunhu hweiyo radicals. Izvi zvimiro zvinowanzoitika mumapuroteni etransmembrane akaiswa mu lipid bilayer membrane yakatenderedza maseru. Nzvimbo dze hydrophobic dzemapuroteni dzinoramba dzakagadzikana mukati mechikamu chemafuta che membrane, nepo nzvimbo dze hydrophilic dzeprotein dzinosangana nemhepo ine mvura kumativi ose maviri.

Zvakare, kugadzikana kwezvivakwa zvepamusoro kunovimbiswa nehurefu-refu zvisungo pakati peamino acids. Muenzaniso wekare wekubatana kwakadaro disulfide zambuko, inowanzoitika pakati pema cysteine ​​​​radicals maviri. Kana iwe wakanzwa chimwe chinhu chakaita senge mazai akaora mu salon yebvudzi panguva yeperm maitiro pabvudzi remutengi, saka iyi yaive chikamu chechimiro chepamusoro cheiyo keratin iri mubvudzi, iyo inoitika kuburikidza nekuderedzwa kwe disulfide zvisungo ne rubatsiro rwesarufa-ine thiol misanganiswa.

Chimiro chepamusoro chinogadziriswa nekudyidzana kwakareba senge hydrophobicity kana disulfide bond.

Disulfide zvisungo zvinogona kuitika pakati cysteine radicals mune imwecheteyo polypeptide cheni, kana pakati pemacysteines kubva kumaketani akasiyana akazara. Kudyidzana pakati pemaketani akasiyana anoumba quaternary chiyero cheprotein chimiro. Muenzaniso wakanakisa weiyo quaternary chimiro hemoglobin iri muropa rako. Imwe molecule yehemoglobin ine maglobin mana akafanana, mapuroteni zvikamu, chimwe nechimwe chazvo chakabatwa munzvimbo chaiyo mukati mepolypeptide nemabhiriji edisulfide, uye zvakare chinobatanidzwa neheme molecule ine iron. Ese maglobins mana akabatana nemabhiriji e-intermolecular disulfide, uye morekuru rese rinosunga kune akati wandei emhepo mamorekuru kamwechete, kusvika mana, uye rinokwanisa kuasunungura sezvinodiwa.

Modelling zvimiro mukutsvaga mushonga wechirwere

Cheni dzepolypeptide dzinotanga kupeta kuita chimiro chadzo chekupedzisira panguva yekushandura, sezvo cheni inokura ichibuda mu ribosome, senge chidimbu chewaya yendangariro-alloy inogona kutora maumbirwo akaomarara kana yapiswa. Nekudaro, senguva dzose mubiology, zvinhu hazvisi nyore kudaro.

Mumasero mazhinji, majini akanyorwa anogadziridzwa zvakanyanya isati yaturikirwa, ichichinja zvakanyanya chimiro cheprotein kana ichienzaniswa neyakajeka base sequence yejini. Muchiitiko ichi, nzira dzekushandura dzinowanzokumbira rubatsiro rwema molecular chaperones, mapuroteni anosunga kwenguva pfupi kune nascent polypeptide cheni uye anodzivirira kuti irege kutora chero fomu yepakati, kubva kwavanenge vasingazokwanisi kuenda kune yekupedzisira.

Izvi zvese kutaura kuti kufanotaura chimiro chekupedzisira cheprotein harisi basa diki. Kwemakumi emakore, nzira chete yekudzidza chimiro chemapuroteni yaive kuburikidza nemaitiro emuviri akadai seX-ray crystallography. Yakanga isiri kusvika pakupera kwema1960s apo biophysical chemist yakatanga kuvaka computational modhi yeprotein kupeta, kunyanya kutarisa kune yechipiri chimiro modhi. Nzira idzi nevazukuru vadzo dzinoda huwandu hukuru hwe data yekuisa mukuwedzera kune yekutanga chimiro - semuenzaniso, matafura eamino acid bond angles, rondedzero ye hydrophobicity, inochajirwa nyika, uye kunyangwe kuchengetedzwa kwechimiro uye basa pamusoro pekushanduka-shanduka kwenguva - zvese kuitira fungidzira kuti chii chichaitika senge protein yekupedzisira.

Mazuva ano nzira dzemakombuta dzekufanotaura kwechipiri chimiro, senge idzo dzinomhanya paFolding@Home network, inoshanda neinosvika makumi masere muzana echokwadi - izvo zvakanaka chaizvo tichitarisa kuoma kwedambudziko. Dhata inogadzirwa nemamodhi ekufungidzira pamapuroteni akadai seSARS-CoV-80 spike protein inofananidzwa nedata kubva kuzvidzidzo zvemuviri zvehutachiona. Nekuda kweizvozvo, zvinokwanisika kuwana iyo chaiyo chimiro cheprotein uye, pamwe, kunzwisisa kuti hutachiona hunonamatira sei kune receptors. Angiotensin inoshandura enzyme 2 munhu ari munzira yekufema inoenda mumuviri. Kana tikakwanisa kuona chimiro ichi, tinogona kuwana mishonga inovhara kusunga uye kudzivirira utachiona.

Protein kupeta tsvagiridzo iri pamwoyo wekunzwisisa kwedu kwezvirwere zvakawanda uye hutachiona zvekuti kunyangwe isu tikashandisa iyo Folding@Home network kufunga nzira yekukunda COVID-19, iyo yatakaona ichiputika mukukura nguva pfupi yadarika, network haigone. kushanda kwenguva refu. Icho chishandiso chekutsvagisa chakanyatsokodzera pakudzidza mapuroteni anokonzera zvirwere zvakawanda zveprotein misfolding, sengechirwere cheAlzheimer kana chirwere cheCreutzfeldt-Jakob, chinowanzonzi chirwere chemombe chinopenga. Uye apo humwe utachiona hukangooneka, tichange tagadzirira kutanga kurwisana nahwo zvakare.

Source: www.habr.com