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Mphotho ya Lasker Basic Medical Research ya chaka chino idaperekedwa kwa Demis Hassabis ndi John Jumper chifukwa cha zopereka zawo popanga dongosolo lanzeru la AlphaFold lomwe limaneneratu kapangidwe ka magawo atatu a mapuloteni potengera dongosolo loyamba la ma amino acid.

Zotsatira zawo zimathetsa vuto lomwe lasautsa asayansi kwa nthawi yayitali ndikutsegula chitseko chofulumizitsa kafukufuku m'magawo onse azachipatala. Mapuloteni amagwira ntchito yofunika kwambiri pakukula kwa matenda: mu matenda a Alzheimer's, amapindika ndikuphatikizana; Mu khansa, ntchito yawo yoyang'anira imatayika; Mu chibadwa kagayidwe kachakudya matenda, iwo ndi kukanika; Mu cystic fibrosis, amapita kumalo olakwika mu selo. Izi ndi zochepa chabe mwa njira zambiri zomwe zimayambitsa matenda. Mitundu yatsatanetsatane yamapuloteni imatha kupereka masanjidwe a atomiki, kuyendetsa mapangidwe kapena kusankha mamolekyu ogwirizana kwambiri, ndikufulumizitsa kupezeka kwa mankhwala.

Mapangidwe a mapuloteni nthawi zambiri amatsimikiziridwa ndi X-ray crystallography, nyukiliya maginito resonance ndi cryo-electron microscopy. Njira zimenezi ndi zodula komanso zimatenga nthawi. Izi zimapangitsa kuti pakhale nkhokwe zama protein za 3D zomwe zili ndi data pafupifupi 200,000 zokha, pomwe ukadaulo wotsatizana wa DNA wapanga ma proteni opitilira 8 miliyoni. M'zaka za m'ma 1960, Anfinsen et al. adapeza kuti mndandanda wa 1D wa ma amino acid ukhoza kupindika modzidzimutsa komanso mobwerezabwereza kukhala mawonekedwe azithunzi zitatu (Chithunzi 1A), komanso kuti ma molekyulu "otsogolera" amatha kufulumizitsa ndikuwongolera izi. Zomwe taziwonazi zimadzetsa vuto lazaka 60 mu biology ya mamolekyulu: kulosera za 3D kapangidwe ka mapuloteni kuchokera mu mndandanda wa 1D wa ma amino acid. Ndi kupambana kwa Project ya Human Genome, kuthekera kwathu kupeza ma amino acid a 1D kwapita patsogolo kwambiri, ndipo vutoli lakhala lofunika kwambiri.

Kulosera mapangidwe a mapuloteni ndizovuta pazifukwa zingapo. Choyamba, malo onse otheka a mbali zitatu a atomu iliyonse mu amino acid amafunikira kufufuza kwambiri. Chachiwiri, mapuloteni amagwiritsa ntchito kwambiri powonjezera pamapangidwe awo amankhwala kuti asinthe maatomu moyenera. Popeza mapuloteni nthawi zambiri amakhala ndi mazana a hydrogen bond "opereka" (kawirikawiri okosijeni) omwe amayenera kukhala pafupi ndi hydrogen bond "acceptor" (kawirikawiri nayitrogeni womangidwa ku haidrojeni), zitha kukhala zovuta kwambiri kupeza ma conformations pomwe pafupifupi wopereka aliyense ali pafupi ndi wolandila. Chachitatu, pali zitsanzo zochepa za maphunziro a njira zoyesera, choncho m'pofunika kumvetsetsa kuyanjana kwa mbali zitatu pakati pa amino acid pamaziko a 1D ndondomeko pogwiritsa ntchito chidziwitso cha kusintha kwa mapuloteni oyenerera.

Fiziki idagwiritsidwa ntchito koyamba kuwonetsa momwe ma atomu amagwirira ntchito pofufuza njira yabwino kwambiri, ndipo njira idapangidwa kuti iwonetsere momwe mapuloteni amapangidwira. Karplus, Levitt ndi Warshel adalandira Mphotho ya Nobel mu Chemistry mu 2013 chifukwa cha ntchito yawo yofananira ndi mapuloteni. Komabe, njira zozikidwa pa fizikisi ndizokwera mtengo ndipo zimafuna kukonzedwa pafupifupi, kotero kuti mawonekedwe enieni amitundu itatu sangathe kulosera. Njira inanso "yotengera chidziwitso" ndiyo kugwiritsa ntchito nkhokwe zamapangidwe odziwika ndi njira zophunzitsira anthu pogwiritsa ntchito luntha lochita kupanga komanso kuphunzira pamakina (AI-ML). Hassabis ndi Jumper amagwiritsa ntchito zinthu zonse zafizikiki ndi AI-ML, koma kutsogola ndi kudumpha kwa magwiridwe antchito kumachokera ku AI-ML. Ofufuza awiriwa adaphatikiza mwaluso ma database akuluakulu a anthu ndi zida zamakompyuta zamafakitale kuti apange AlphaFold.

Kodi tikudziwa bwanji kuti "athetsa" chithunzithunzi cholosera? Mu 1994, mpikisano wa Critical Assessment of Structure Prediction (CASP) unakhazikitsidwa, womwe umakumana zaka ziwiri zilizonse kuti awone momwe kulosera kwapangidwe. Ofufuzawo adzagawana nawo 1D yotsatizana ya mapuloteni omwe mawonekedwe awo adawathetsa posachedwa, koma zotsatira zake sizinasindikizidwe. Wolosera amalosera mawonekedwe amitundu itatu pogwiritsa ntchito njira ya 1D iyi, ndipo woyesayo amaweruza mozama za zotsatira zomwe zanenedweratu poziyerekeza ndi mawonekedwe amitundu itatu omwe amaperekedwa ndi woyeserera (wongoperekedwa kwa wowunika). CASP imapanga ndemanga zenizeni zakhungu ndikulemba kulumpha kwanthawi ndi nthawi komwe kumakhudzana ndi luso laukadaulo. Pamsonkhano wa 14 wa CASP mu 2020, zolosera za AlphaFold zidawonetsa kudumphadumpha kotero kuti okonza adalengeza kuti vuto la kulosera za 3D lathetsedwa: kulondola kwa maulosi ambiri kunali pafupi ndi kuyesako.

Kufunika kokulirapo ndikuti ntchito ya Hassabis ndi Jumper ikuwonetsa motsimikizika momwe AI-ML ingasinthire sayansi. Kafukufuku wake akuwonetsa kuti AI-ML imatha kupanga malingaliro ovuta asayansi kuchokera kumagwero angapo a data, kuti njira zowunikira (zofanana ndi zomwe zili mu ChatGPT) zitha kupeza kudalira kwakukulu ndi kulumikizana komwe kumachokera ku data, komanso kuti AI-ML ikhoza kudziweruza yokha momwe zotsatira zake zimatuluka. AI-ML ikuchita sayansi kwenikweni.