labarai

An ba Demis Hassabis da John Jumper lambar yabo ta Lasker Basic Medical Research Award na wannan shekara saboda gudummawar da suka bayar wajen samar da tsarin fasaha na AlphaFold na wucin gadi wanda ya yi hasashen tsarin furotin mai girma uku bisa tsarin farko na amino acid.

Sakamakonsu ya warware matsalar da ta dade tana damun al'ummar kimiyya tare da bude kofa ga hanzarta gudanar da bincike a fannin nazarin halittu. Sunadaran suna taka muhimmiyar rawa wajen haɓaka cututtuka: a cikin cutar Alzheimer, suna ninka kuma suna haɗuwa tare; A cikin ciwon daji, aikin sarrafa su ya ɓace; A cikin cututtuka na rayuwa na rayuwa, sun kasance marasa aiki; A cikin cystic fibrosis, suna shiga cikin sarari mara kyau a cikin tantanin halitta. Waɗannan kaɗan ne daga cikin hanyoyin da ke haifar da cututtuka. Cikakken tsarin tsarin furotin na iya samar da jeri na atomic, fitar da ƙira ko zaɓin manyan ƙwayoyin cuta, da haɓaka gano magunguna.

Tsarin sunadaran gabaɗaya ana ƙaddara su ta hanyar crystallography X-ray, ƙarfin maganadisu na nukiliya da microscopy na cryo-electron. Waɗannan hanyoyin suna da tsada kuma suna ɗaukar lokaci. Wannan yana haifar da bayanan tsarin furotin na 3D masu wanzuwa tare da bayanan tsarin kusan 200,000 kawai, yayin da fasahar jerin DNA ta samar da jerin sunadaran gina jiki sama da miliyan 8. A cikin 1960s, Anfinsen et al. An gano cewa jerin amino acid na 1D na iya naɗa kai tsaye kuma akai-akai a ninka su cikin daidaituwa mai girma uku (Hoto na 1A), kuma “chaperones” na ƙwayoyin cuta na iya haɓakawa da sauƙaƙe wannan tsari. Waɗannan abubuwan lura suna haifar da ƙalubalen shekaru 60 a cikin ilmin halitta: tsinkaya tsarin 3D na sunadaran daga jerin 1D na amino acid. Tare da nasarar aikin Tsarin Halittar Dan Adam, ikonmu na samun jerin amino acid na 1D ya inganta sosai, kuma wannan ƙalubalen ya ƙara zama cikin gaggawa.

Hasashen tsarin furotin yana da wahala saboda dalilai da yawa. Na farko, duk matsayi mai girma uku na kowane zarra a cikin kowane amino acid yana buƙatar bincike mai yawa. Na biyu, sunadaran suna yin iyakar yin amfani da abubuwan da suka dace a cikin tsarinsu na sinadarai don daidaita atom yadda ya kamata. Tunda sunadaran yawanci suna da ɗaruruwan haɗin hydrogen “masu ba da gudummawa” (yawanci oxygen) waɗanda yakamata su kasance kusa da haɗin haɗin hydrogen “mai karɓa” (yawanci nitrogen daure da hydrogen), yana iya zama da wahala a sami daidaituwa inda kusan kowane mai bayarwa yana kusa da mai karɓa. Na uku, akwai ƙayyadaddun misalai don horar da hanyoyin gwaji, don haka wajibi ne a fahimci yuwuwar mu'amala mai girma uku tsakanin amino acid bisa tsarin 1D ta amfani da bayanai kan juyin halittar sunadarai masu dacewa.

An fara amfani da Physics don yin ƙirar hulɗar atom a cikin neman mafi kyawun daidaituwa, kuma an samar da wata hanya don hango ko hasashen tsarin sunadaran. Karplus, Levitt da Warshel an ba su lambar yabo ta Nobel ta 2013 a cikin Chemistry saboda aikinsu kan kwaikwaiyon sunadarai. Koyaya, hanyoyin tushen ilimin kimiyyar lissafi suna da tsadar ƙididdiga kuma suna buƙatar ƙimanta aiki, don haka ba za a iya hasashen madaidaicin tsari mai girma uku ba. Wata hanyar “tushen ilimi” ita ce yin amfani da bayanan bayanai na sanannun sifofi da jeri don horar da ƙira ta hanyar basirar ɗan adam da koyan inji (AI-ML). Hassabis da Jumper suna amfani da abubuwa na kimiyyar lissafi da AI-ML, amma ƙirƙira da tsalle cikin aiwatar da tsarin sun samo asali ne daga AI-ML. Masu binciken guda biyu sun haɗa manyan bayanan jama'a tare da albarkatun lissafin masana'antu don ƙirƙirar AlphaFold.

Ta yaya za mu san sun “warware” da wuyar warwarewar tsarin? A cikin 1994, an kafa gasa ta Critical Assessment of Structure Prediction (CASP), wacce ke haduwa kowace shekara biyu don bin diddigin ci gaban hasashen tsarin. Masu binciken za su raba jerin 1D na furotin wanda tsarinsa kwanan nan suka warware, amma wanda ba a buga sakamakonsa ba. Mai tsinkaya yana tsinkayar tsari mai girma uku ta amfani da wannan jeri na 1D, kuma mai kimantawa da kansa yana yin hukunci da ingancin sakamakon da aka annabta ta hanyar kwatanta su da tsarin girma uku da mai gwaji ya bayar (wanda aka bayar ga mai kimantawa kawai). CASP tana gudanar da bita na makafi na gaskiya kuma tana yin rikodin tsalle-tsalle na lokaci-lokaci da ke da alaƙa da sabbin hanyoyin. A taron CASP na 14th a cikin 2020, sakamakon Hasashen AlphaFold ya nuna irin wannan tsalle-tsalle a cikin aiki wanda masu shirya suka ba da sanarwar cewa an warware matsalar hasashen tsarin 3D: daidaiton yawancin tsinkaya yana kusa da na ma'aunin gwaji.

Babban mahimmanci shine aikin Hassabis da Jumper yana nuna gamsuwa yadda AI-ML zata iya canza kimiyya. Bincikensa ya nuna cewa AI-ML na iya gina hadaddun hasashen kimiyya daga tushen bayanai da yawa, cewa hanyoyin kulawa (kamar waɗanda ke cikin ChatGPT) na iya gano mahimman abubuwan dogaro da alaƙa a cikin hanyoyin bayanai, kuma AI-ML na iya yin hukunci da kansa akan ingancin sakamakon fitarwa. AI-ML yana yin kimiyya da gaske.