Ndiye kodi "kupinda kwa mapuloteni" ndi chiyani kwenikweni?

Mliri wapano wa COVID-19 wadzetsa mavuto ambiri omwe obera akhala okondwa kuwaukira. Kuchokera ku zishango za nkhope zosindikizidwa za 3D ndi masks azachipatala opangidwa kunyumba kuti alowe m'malo mwa makina olowera mpweya, kutulutsa kwamalingaliro kunali kolimbikitsa komanso kolimbikitsa. Nthawi yomweyo, panali zoyesayesa zopita patsogolo kudera lina: mu kafukufuku wolimbana ndi kachilombo komweko.

Mwachiwonekere, kuthekera kwakukulu koyimitsa mliri wapano ndi kupitilira onse omwe akutsata ndi njira yomwe ikuyesera kufikira komwe kumayambitsa vutoli. Njira ya "kudziwa mdani wanu" imatengedwa ndi Folding@Home computing project. Anthu mamiliyoni ambiri adalembetsa nawo ntchitoyi ndipo akupereka mphamvu zina zopangira ma processor awo ndi ma GPU, motero akupanga makompyuta apamwamba kwambiri [ogawidwa] m'mbiri.

Koma kodi ma exaflops onsewa amagwiritsidwa ntchito bwanji? Chifukwa chiyani kuli kofunikira kuponya mphamvu yamakompyuta yotere mapuloteni opinda? Ndi mtundu wanji wa biochemistry womwe ukugwira ntchito pano, chifukwa chiyani mapuloteni amafunikira kupindika? Nayi mwachidule mwachidule pakupinda kwa mapuloteni: chomwe ndi, momwe zimachitikira, komanso chifukwa chake ndizofunikira.

Choyamba, chofunikira kwambiri: chifukwa chiyani mapuloteni amafunikira?

Mapuloteni ndi zinthu zofunika kwambiri. Sikuti amangopereka zomangira zama cell, komanso amagwiranso ntchito ngati chothandizira ma enzyme pafupifupi zonse zomwe zimachitika mthupi. Agologolo, akhale iwo zomangika kapena enzymatic, ndi maunyolo aatali amino acid, yomwe ili mumndandanda wakutiwakuti. Ntchito zamapuloteni zimatsimikiziridwa ndi ma amino acid omwe amapezeka m'malo ena pamapuloteni. Ngati, mwachitsanzo, puloteni ikufunika kumangiriza ku molekyulu yoyendetsedwa bwino, malo omangirawo ayenera kudzazidwa ndi ma amino acid omwe ali ndi vuto loyipa.

Kuti timvetse mmene mapulotini amapezera kamangidwe kake kamene kamatsimikizira ntchito yake, tifunika kusanthula mfundo zoyambira za mamolekyulu a zinthu zamoyo ndi mmene zinthu zimayendera mu selo.

Kupanga, kapena mawu mapuloteni amayamba ndi ndondomekoyi zolemba. Panthawi yolemba, DNA double helix, yomwe ili ndi chidziwitso cha chibadwa cha selo, imamasuka pang'ono, zomwe zimapangitsa kuti maziko a nitrogen a DNA apezeke ku enzyme yotchedwa. RNA polymerase. Ntchito ya RNA polymerase ndiyo kupanga kopi ya RNA, kapena transcript, ya jini. Kope ili la jini lotchedwa mthenga RNA (mRNA), ndi molekyu imodzi yabwino kuwongolera mafakitale a protein, ribosomesomwe akugwira ntchito yopanga, kapena kuwulutsa mapuloteni.

Ma ribosomes amachita ngati makina ophatikiza - amatenga template ya mRNA ndikuyifananitsa ndi tiziduswa tating'ono ta RNA, Kusintha kwa RNA (tRNA). TRNA iliyonse ili ndi zigawo ziwiri zogwira ntchito - gawo la maziko atatu otchedwa anticodon, zomwe ziyenera kufanana ndi ma codons a mRNA, ndi malo omangirira amino acid okhudzana ndi izi. kodi. Pomasulira, mamolekyu a tRNA mu ribosome amayesa kumangirira ku mRNA pogwiritsa ntchito ma anticodon. Ngati zikuyenda bwino, molekyulu ya tRNA imamangirira amino acid yake ku yam'mbuyo, ndikupanga ulalo wotsatira mu unyolo wa ma amino acid osungidwa ndi mRNA.

Kutsatizana kwa ma amino acid ndi gawo loyamba la dongosolo lamapuloteni, chifukwa chake limatchedwa. dongosolo loyamba. Mapangidwe onse atatu a puloteni ndi ntchito zake zimachokera mwachindunji ku kapangidwe kake, ndipo zimadalira zinthu zosiyanasiyana za amino acid ndi machitidwe awo. Popanda mankhwala awa ndi kuyanjana kwa amino acid, ma polypeptides iwo akanakhalabe mizere mizere popanda dongosolo la mbali zitatu. Izi zitha kuwoneka nthawi iliyonse mukaphika chakudya - munjira iyi pali kutentha denaturation mapangidwe atatu azithunzi za mapuloteni.

Zomangira zazitali zama protein

Mulingo wotsatira wa mawonekedwe amitundu itatu, kupitilira woyambayo, adapatsidwa dzina lanzeru dongosolo lachiwiri. Zimaphatikizapo zomangira za haidrojeni pakati pa ma amino acid omwe ali pafupi kwambiri. Chofunikira chachikulu pakulumikizana kokhazikika uku kumabwera kuzinthu ziwiri: alpha helices и mndandanda wa beta. Alpha helix imapanga gawo lopindika kwambiri la polypeptide, pomwe pepala la beta limapanga dera losalala komanso lalikulu. Mapangidwe onsewa ali ndi mawonekedwe komanso magwiridwe antchito, kutengera mawonekedwe a ma amino acid omwe ali nawo. Mwachitsanzo, ngati alpha helix imakhala ndi ma hydrophilic amino acid, monga arginine kapena lysine, ndiye kuti itenga nawo gawo pazochita zamadzi.

Alpha helices ndi mapepala a beta mu mapuloteni. Zomangira za haidrojeni zimapanga panthawi ya mapuloteni.

Mapangidwe awiriwa ndi kuphatikiza kwawo kumapanga gawo lotsatira la kapangidwe ka mapuloteni - maphunziro apamwamba. Mosiyana ndi zidutswa zosavuta zamapangidwe achiwiri, mapangidwe apamwamba amakhudzidwa makamaka ndi hydrophobicity. Pakatikati mwa mapuloteni ambiri amakhala ndi ma hydrophobic amino acid, monga alanine kapena mankhwala methionine, ndipo madzi amachotsedwa kumeneko chifukwa cha "mafuta" amtundu wa radicals. Mapangidwe awa nthawi zambiri amawonekera mu mapuloteni a transmembrane ophatikizidwa mu lipid bilayer nembanemba yozungulira ma cell. Magawo a hydrophobic a mapuloteni amakhalabe okhazikika pa thermodynamically mkati mwa gawo lamafuta la nembanemba, pomwe madera a hydrophilic a mapuloteni amakumana ndi chilengedwe chamadzi kumbali zonse ziwiri.

Komanso, kukhazikika kwa zomangamanga zapamwamba kumatsimikiziridwa ndi maubwenzi aatali pakati pa amino acid. Chitsanzo chodziwika bwino cha kugwirizana koteroko ndi disulfide mlatho, nthawi zambiri zimachitika pakati pa ma cysteine ​​​​radicals awiri. Ngati mumamva fungo lofanana ndi mazira ovunda mu salon ya tsitsi panthawi ya perm pa tsitsi la kasitomala, ndiye kuti ichi chinali chithunzithunzi chapamwamba cha keratin chomwe chili mu tsitsi, chomwe chimachitika chifukwa cha kuchepa kwa zomangira za disulfide ndi chithandizo chokhala ndi sulfure thiol zosakaniza.

Mapangidwe apamwamba amakhazikika ndi kuyanjana kwakutali monga hydrophobicity kapena disulfide bond.

Zomangira za disulfide zitha kuchitika pakati cysteine ma radicals mu unyolo wa polypeptide womwewo, kapena pakati pa ma cysteines ochokera ku maunyolo osiyanasiyana. Kuyanjana pakati pa maunyolo osiyanasiyana kumapanga wachinayi mlingo wa mapuloteni kapangidwe. Chitsanzo chabwino kwambiri cha kapangidwe ka quaternary ndi hemogulobini izo ziri mu mwazi wanu. Molekyu iliyonse ya himogulobini imakhala ndi ma globin anayi ofanana, zigawo za mapuloteni, zomwe zimayikidwa pamalo enaake mkati mwa polypeptide ndi milatho ya disulfide, komanso zimagwirizanitsidwa ndi molekyulu ya heme yokhala ndi chitsulo. Ma globin onse anayi amalumikizidwa ndi milatho ya intermolecular disulfide, ndipo molekyulu yonseyo imamangiriza ku mamolekyu angapo a mpweya nthawi imodzi, mpaka anayi, ndipo imatha kumasula ngati pakufunika.

Kupanga zitsanzo pofunafuna chithandizo cha matenda

Unyolo wa polypeptide umayamba kupindika kukhala mawonekedwe ake omaliza pakumasulira, pomwe unyolo womwe ukukulira umatuluka mu ribosome, monga momwe waya wa memory-alloy amatha kutenga mawonekedwe ovuta akatenthedwa. Komabe, monga nthawi zonse mu biology, zinthu sizili zophweka.

M'maselo ambiri, majini olembedwa amasinthidwa kwambiri asanamasuliridwe, kusintha kwambiri mapangidwe a mapuloteni poyerekeza ndi ndondomeko yeniyeni ya jini. Pachifukwa ichi, njira zomasulira nthawi zambiri zimapempha thandizo la ma chaperones a maselo, mapuloteni omwe amamangiriza kwakanthawi ku unyolo wa polypeptide wa nascent ndikuletsa kutenga mawonekedwe aliwonse apakatikati, pomwe sangathe kupita komaliza.

Izi zikutanthauza kuti kulosera mawonekedwe omaliza a puloteni si ntchito yaing'ono. Kwa zaka zambiri, njira yokhayo yophunzirira kapangidwe ka mapuloteni inali kudzera munjira zakuthupi monga X-ray crystallography. Sizinafike mpaka kumapeto kwa zaka za m'ma 1960 pomwe akatswiri a zamankhwala a biophysical adayamba kupanga mitundu yofananira yamapuloteni, makamaka makamaka pamapangidwe achiwiri. Njirazi ndi mbadwa zawo zimafunikira kuchuluka kwazinthu zolowetsamo kuwonjezera pa kapangidwe kake - mwachitsanzo, matebulo a ma amino acid bond angles, mindandanda ya hydrophobicity, maiko otsogola, komanso kusungidwa kwa kapangidwe ndi magwiridwe antchito munthawi yachisinthiko - zonse kuti zitheke. ganizirani zomwe zidzachitike zidzawoneka ngati mapuloteni omaliza.

Masiku ano njira zowerengera zolosera zachiwiri, monga zomwe zikuyenda pa netiweki ya Folding@Home, zimagwira ntchito molondola pafupifupi 80% - zomwe ndi zabwino kwambiri poganizira zovuta za vutoli. Zambiri zopangidwa ndi mitundu yolosera zam'mapuloteni monga SARS-CoV-2 spike protein zidzafaniziridwa ndi zomwe zachokera kumaphunziro akuthupi a kachilomboka. Zotsatira zake, zidzakhala zotheka kupeza mawonekedwe enieni a mapuloteniwo ndipo, mwina, kumvetsetsa momwe kachilomboka kamamangirira ku zolandilira. angiotensin converting enzyme 2 munthu ali mu kupuma thirakiti lolowera m'thupi. Ngati titha kudziwa kapangidwe kameneka, titha kupeza mankhwala omwe amaletsa kumangirira ndikupewa matenda.

Kafukufuku wopindika mapuloteni ndiye pamtima pakumvetsetsa kwathu matenda ndi matenda ambiri kotero kuti ngakhale titagwiritsa ntchito netiweki ya Folding@Home kuti tidziwe momwe tingagonjetsere COVID-19, yomwe taona ikuphulika posachedwapa, maukonde satero. ndikhale nthawi yayitali osagwira ntchito. Ndi chida chofufuzira chomwe chili choyenera kwambiri pofufuza za matenda a protein omwe amayambitsa matenda ambiri osokonekera ndi mapuloteni, monga matenda a Alzheimer's kapena matenda a Creutzfeldt-Jakob, omwe nthawi zambiri amatchedwa matenda amisala a ng'ombe. Ndipo pamene kachilombo kena kuonekera mosapeŵeka, tidzakhala okonzeka kuyambanso kulimbana nacho.

Source: www.habr.com