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Mubairo wegore rino weLasker Basic Medical Research Award wakapihwa kuna Demis Hassabis naJohn Jumper nekuda kwekubatsira kwavo mukusikwa kweAlphaFold artificial intelligence system inofanotaura chimiro chemativi matatu emapuroteni zvichibva pakutevedzana kwekutanga kwemaamino acids.

Mhedzisiro yavo inogadzirisa dambudziko ragara richinetsa nharaunda yesainzi uye kuvhura musuwo wekukurumidza kutsvagisa munzvimbo yebiomedical. Mapuroteni anoita basa rakakosha mukukura kwechirwere: muchirwere cheAlzheimer, anopeta uye anobatana pamwechete; Mukenza, basa ravo rekutonga rinorasika; Mukusagadzikana kwemetabolism, ivo havashande; Mu cystic fibrosis, vanopinda munzvimbo isiriyo muchitokisi. Aya angori mashoma enzira dzakawanda dzinokonzera zvirwere. Yakadzama mapuroteni maitiro emhando anogona kupa maatomu ekumisikidza, kutyaira dhizaini kana kusarudzwa kweakakwira-affinity mamorekuru, uye nekumhanyisa kuwanikwa kwezvinodhaka.

Zvimiro zveprotein zvinowanzotemwa neX-ray crystallography, nuclear magnetic resonance uye cryo-electron microscopy. Nzira idzi dzinodhura uye dzinotora nguva. Izvi zvinokonzeresa iripo 3D mapuroteni echimiro dhatabhesi ane angangoita mazana maviri ezviuru data data, nepo tekinoroji yeDNA yakaburitsa mapuroteni anodarika mamirioni masere. Muma1960, Anfinsen et al. yakawana kuti 1D kutevedzana kwemaamino acids inogona kupeta nekungopeta kuita matatu-dimensional conformation (Mufananidzo 1A), uye kuti mamorekuru "chaperones" anogona kukurumidza uye kufambisa maitiro aya. Izvi zvinotarisisa zvinotungamira kune 60-gore dambudziko mune molecular biology: kufanotaura iyo 3D chimiro chemapuroteni kubva ku1D kutevedzana kwemaamino acids. Nekubudirira kweHuman Genome Project, kugona kwedu kuwana 1D amino acid kutevedzana kwave nani, uye dambudziko iri rave nekukasira.

Kufanotaura mapuroteni maitiro kwakaoma kune zvikonzero zvakawanda. Chekutanga, ese anogoneka matatu-dimensional zvinzvimbo zveatomu yega yega mune yega amino acid inoda kuongororwa kwakawanda. Chechipiri, mapuroteni anoshandisa zvakanyanya kuwirirana muchimiro chavo chemakemikari kunyatsogadzirisa maatomu. Sezvo mapuroteni achiwanzova nemazana ehydrogen bond "vanopa" (kazhinji okisijeni) iyo inofanirwa kunge iri padyo nehydrogen bond "acceptor" (kazhinji nitrogen inosungirirwa kuhydrogen), zvinogona kunetsa kuwana conformations apo anenge mupi wese ari pedyo nemugamuchiri. Chechitatu, kune mienzaniso mishoma yekudzidziswa kwemaitiro ekuyedza, saka zvinodikanwa kuti tinzwisise zvingangoitika zvitatu-dimensional kudyidzana pakati peamino acids pahwaro hwe1D kutevedzana uchishandisa ruzivo rwekushanduka kwemapuroteni akakodzera.

Fizikisi yakatanga kushandiswa kuenzanisira kupindirana kwemaatomu mukutsvaga kuenderana kwakanakisa, uye nzira yakagadziridzwa kufanotaura chimiro chemapuroteni. Karplus, Levitt naWarshel vakapihwa mubairo weNobel muChemistry muna 2013 nekuda kwebasa ravo rekuita computational simulation yemapuroteni. Nekudaro, nzira dzakavakirwa pafizikisi dzinodhura zvakanyanya uye dzinoda kufungidzira kugadziridzwa, saka chaiyo-matatu-dimensional zvimiro hazvigone kufanotaurwa. Imwe nzira "yeruzivo-yakavakirwa" ndeye kushandisa dhatabhesi yezvivakwa zvinozivikanwa uye kutevedzana kudzidzisa modhi kuburikidza nehungwaru hwekugadzira uye muchina kudzidza (AI-ML). Hassabis uye Jumper vanoshandisa zvinhu zveese ari maviri fizikisi neAI-ML, asi hutsva uye kusvetuka mukuita kwemaitiro kunobva zvakanyanya kubva kuAI-ML. Vatsvagiri vaviri ava vakasanganisa dhatabhesi hombe dzeveruzhinji neindasitiri-giredhi komputa zviwanikwa kugadzira AlphaFold.

Tinoziva sei kuti "vakagadzirisa" dhizaini yekufanotaura? Muna 1994, makwikwi eCritical Assessment of Structure Prediction (CASP) akamiswa, ayo anosangana makore maviri ega ega kuronda mafambiro ekufanotaura kwezvimiro. Vatsvagiri vanozogovera iyo 1D kutevedzana kweprotein ine chimiro chavakagadzirisa munguva pfupi yapfuura, asi izvo zvabuda hazvisati zvaburitswa. Mutariri anofanotaura chimiro chetatu-dimensional achishandisa iyi 1D kutevedzana, uye muongorori anotonga akazvimirira ega kunaka kwezvakafanotaurwa nekuzvienzanisa neatatu-dimensional chimiro chakapihwa nemuongorori (akapihwa chete kumuongorori). CASP inoitisa mapofu echokwadi uye inorekodha periodic performance inosvetuka ine chekuita nemethodological innovation. PaMusangano wechigumi nemana weCASP muna 2020, mhedzisiro yekufanotaura kweAlphaFold yakaratidza kusvetuka mukuita zvekuti varongi vakazivisa kuti dambudziko rekufanotaura kwechimiro che3D rakanga ragadziriswa: chokwadi chekufungidzira kwakawanda kwaive pedyo neicho chekuyedza kuyerwa.

Izvo zvakakosha ndezvekuti basa raHassabis naJumper rinoratidza zvinogutsa kuti AI-ML ingashandura sei sainzi. Tsvagiridzo yayo inoratidza kuti AI-ML inogona kuvaka fungidziro dzakaomarara dzesainzi kubva kune akawanda data masosi, kuti nzira dzekutarisisa (dzakafanana neidzo dziri muChatGPT) dzinogona kuwana zvakakosha zvinotsamira uye kuwirirana mune zvinyorwa zvedata, uye kuti AI-ML inogona kuzvitonga yega mhando yezvainoburitsa. AI-ML iri kuita sainzi.