Xyoo no Lasker Basic Medical Research Award tau muab tsub rau Demis Hassabis thiab John Jumper rau lawv txoj kev koom tes rau kev tsim AlphaFold kev txawj ntse kev txawj ntse uas kwv yees peb-dimensional qauv ntawm cov proteins raws li thawj qhov kev txiav txim ntawm cov amino acids.
Lawv cov txiaj ntsig tau daws qhov teeb meem uas tau ua rau lub zej zog kev tshawb fawb ntev ntev thiab qhib qhov rooj kom nrawm rau kev tshawb fawb thoob plaws biomedical. Proteins ua lub luag haujlwm tseem ceeb hauv kev txhim kho kab mob: hauv Alzheimer's kab mob, lawv quav thiab clump ua ke; Hauv kev mob qog noj ntshav, lawv cov kev tswj hwm kev ua haujlwm tau ploj lawm; Hauv kev yug menyuam hauv cov kab mob metabolic, lawv tsis ua haujlwm; Hauv cystic fibrosis, lawv nkag mus rau hauv qhov chaw tsis ncaj ncees lawm hauv lub cell. Cov no tsuas yog qee qhov ntawm ntau cov txheej txheem uas ua rau muaj kab mob. Cov qauv tsim cov protein ntau tuaj yeem muab cov kev teeb tsa atomic, tsav kev tsim lossis xaiv cov molecules high-affinity molecules, thiab ceev cov tshuaj nrhiav pom.
Cov qauv protein feem ntau txiav txim siab los ntawm X-ray crystallography, nuclear magnetic resonance thiab cryo-electron microscopy. Cov txheej txheem no yog kim thiab siv sijhawm ntev. Qhov no ua rau cov ntaub ntawv 3D protein uas twb muaj lawm nrog tsuas yog txog 200,000 cov ntaub ntawv tsim qauv, thaum DNA sequencing thev naus laus zis tau tsim ntau dua 8 lab cov protein ntau. Hauv xyoo 1960, Anfinsen et al. tshawb pom tias 1D ib ntus ntawm cov amino acids tuaj yeem tshwm sim thiab rov ua dua tshiab rau hauv qhov kev ua haujlwm peb-dimensional conformation (Daim duab 1A), thiab cov molecular "chaperones" tuaj yeem ua kom nrawm thiab pab txhawb cov txheej txheem no. Cov kev soj ntsuam no ua rau muaj kev sib tw 60-xyoo hauv molecular biology: kwv yees cov qauv 3D ntawm cov proteins los ntawm 1D ib ntus ntawm cov amino acids. Nrog rau kev ua tiav ntawm Human Genome Project, peb lub peev xwm kom tau txais 1D amino acid sequences tau txhim kho zoo heev, thiab qhov kev sib tw no tau dhau los ua qhov ceev.
Kev kwv yees cov qauv protein yog qhov nyuaj rau ntau yam. Ua ntej, txhua qhov ua tau peb-dimensional txoj haujlwm ntawm txhua lub atom hauv txhua cov amino acid yuav tsum tau tshawb nrhiav ntau. Qhov thib ob, cov proteins ua rau kev siv ntau tshaj plaws ntawm kev sib ntxiv hauv lawv cov qauv tshuaj kom muaj txiaj ntsig zoo rau cov atoms. Txij li thaum cov proteins feem ntau muaj pua pua ntawm hydrogen daim ntawv cog lus "cov neeg pub" (feem ntau yog cov pa oxygen) uas yuav tsum nyob ze rau hydrogen daim ntawv cog lus "acceptor" (feem ntau nitrogen khi rau hydrogen), nws tuaj yeem nyuaj heev los nrhiav kev sib haum xeeb uas yuav luag txhua tus neeg pub khoom nyob ze rau tus txais. Qhov thib peb, muaj qee qhov piv txwv rau kev cob qhia cov kev sim, yog li nws yuav tsum nkag siab txog qhov muaj peev xwm ntawm peb sab kev sib cuam tshuam ntawm cov amino acids ntawm lub hauv paus ntawm 1D ib ntus siv cov ntaub ntawv ntawm kev hloov pauv ntawm cov proteins uas cuam tshuam.
Physics yog thawj zaug siv los ua qauv kev sib cuam tshuam ntawm atoms hauv kev tshawb nrhiav qhov zoo tshaj plaws conformation, thiab ib txoj kev tau tsim los kwv yees cov qauv ntawm cov proteins. Karplus, Levitt thiab Warshel tau txais 2013 Nobel nqi zog hauv Chemistry rau lawv txoj haujlwm ntawm kev simulation ntawm cov protein. Txawm li cas los xij, physics-raws li txoj hauv kev suav nrog kim kim thiab xav tau kev ua haujlwm kwv yees, yog li cov qauv peb-dimensional tsis tuaj yeem kwv yees. Lwm txoj hauv kev "kev paub txog" yog siv cov ntaub ntawv ntawm cov qauv paub thiab cov kab ke los qhia cov qauv los ntawm kev txawj ntse thiab kev kawm tshuab (AI-ML). Hassabis thiab Jumper siv cov ntsiab lus ntawm physics thiab AI-ML, tab sis kev tsim kho tshiab thiab dhia hauv kev ua tau zoo ntawm txoj hauv kev feem ntau yog los ntawm AI-ML. Ob tus kws tshawb fawb tau tsim tswv yim ua ke cov ntaub ntawv pej xeem loj nrog kev lag luam-qib cov peev txheej los tsim AlphaFold.
Peb yuav ua li cas thiaj paub tias lawv tau "kua tau" cov qauv kev twv ua ntej puzzle? Nyob rau hauv 1994, qhov kev ntsuam xyuas tseem ceeb ntawm cov qauv Prediction (CASP) kev sib tw tau tsim, uas ua tau raws txhua ob xyoos los taug qab qhov kev nce qib ntawm cov qauv kev kwv yees. Cov kws tshawb fawb yuav qhia txog 1D ib ntus ntawm cov protein uas nws cov qauv uas lawv tau daws tsis ntev los no, tab sis nws cov txiaj ntsig tseem tsis tau luam tawm. Tus kwv yees kwv yees tus qauv peb-seem siv qhov 1D kab ke no, thiab tus neeg ntsuam xyuas ntawm nws tus kheej txiav txim siab qhov zoo ntawm cov txiaj ntsig tau los ntawm kev muab piv rau cov qauv peb-seem muab los ntawm tus kws sim (tsuas yog rau tus neeg ntsuam xyuas). CASP ua qhov kev tshuaj xyuas qhov muag tsis pom tseeb thiab sau tseg cov kev ua tau zoo ib ntus cuam tshuam nrog kev tsim kho tshiab. Ntawm 14th CASP Lub Rooj Sib Tham hauv 2020, AlphaFold qhov kev kwv yees tau tshwm sim tau pom zoo li kev nce qib hauv kev ua tau zoo uas cov koom haum tau tshaj tawm tias qhov teeb meem 3D qauv kwv yees tau raug daws: qhov tseeb ntawm qhov kev kwv yees feem ntau ze rau qhov kev sim ntsuas.
Qhov tseem ceeb tshaj plaws yog Hassabis thiab Jumper txoj haujlwm ua kom pom tseeb tias AI-ML tuaj yeem hloov pauv kev tshawb fawb li cas. Nws cov kev tshawb fawb qhia tau hais tias AI-ML tuaj yeem tsim cov kev xav ntawm kev tshawb fawb los ntawm ntau qhov chaw cov ntaub ntawv, cov txheej txheem kev saib xyuas (zoo ib yam li cov hauv ChatGPT) tuaj yeem nrhiav pom qhov tseem ceeb ntawm kev vam khom thiab kev sib raug zoo hauv cov ntaub ntawv, thiab AI-ML tuaj yeem txiav txim siab tus kheej qhov zoo ntawm nws cov txiaj ntsig tso tawm. AI-ML yog qhov tseem ceeb ua kev tshawb fawb.
Post lub sij hawm: Sep-23-2023