amakuru

Uyu mwaka igihembo cya Lasker Basic Medical Research Award cyahawe Demis Hassabis na John Jumper kubera uruhare bagize mu ishyirwaho rya sisitemu y’ubwenge y’ubukorikori ya AlphaFold iteganya imiterere y’ibice bitatu bya poroteyine hashingiwe ku rutonde rwa mbere rwa acide amine.

Ibisubizo byabo bikemura ikibazo kimaze igihe kinini kibangamiye siyanse kandi gifungura umuryango wo kwihutisha ubushakashatsi murwego rwibinyabuzima. Poroteyine zigira uruhare runini mu iterambere ry’indwara: mu ndwara ya Alzheimer, zirazinga kandi zigahurira hamwe; Muri kanseri, imikorere yabo yo kugenzura iratakara; Mu kuvuka kwa metabolike ivuka, ntibikora neza; Muri fibrosis ya cystic, bajya mumwanya utari muto muri selire. Izi ni nkeya muburyo bwinshi butera indwara. Imiterere irambuye ya poroteyine irashobora gutanga ibishushanyo bya atome, gutwara igishushanyo mbonera cyangwa guhitamo molekile nyinshi cyane, no kwihutisha kuvumbura ibiyobyabwenge.

Imiterere ya poroteyine igenwa na X-ray kristallografiya, magnetiki resonance ya kirimbuzi na microscopi ya cryo-electron. Ubu buryo buhenze kandi butwara igihe. Ibi bivamo ububiko bwa poroteyine ya 3D iriho hamwe namakuru agera ku 200.000 gusa yimiterere, mugihe tekinoroji ya ADN ikurikirana itanga poroteyine zirenga miliyoni 8. Mu myaka ya za 1960, Anfinsen n'abandi. yavumbuye ko 1D ikurikiranye ya acide amine ishobora guhita kandi igasubirwamo muburyo bukoreshwa muburyo butatu (Ishusho 1A), kandi ko "chaperone" ya molekile ishobora kwihuta no koroshya iki gikorwa. Izi nyigisho ziganisha ku kibazo cyimyaka 60 muri biologiya ya molekuline: guhanura imiterere ya 3D ya poroteyine kuva 1D ikurikirana ya aside amine. Hamwe nitsinzi ryumushinga wa kimuntu, ubushobozi bwacu bwo kubona 1D aminide acide ikurikirana byateye imbere cyane, kandi iki kibazo cyabaye cyihutirwa.

Guteganya poroteyine biragoye kubwimpamvu nyinshi. Ubwa mbere, ibishoboka byose-bitatu-bya buri atom muri buri aside aside amine bisaba ubushakashatsi bwinshi. Icya kabiri, poroteyine zikoresha cyane kuzuzanya muburyo bwa shimi kugirango zigaragaze neza atome. Kubera ko poroteyine zisanzwe zifite amajana n'amajana ya hydrogène “abaterankunga” (ubusanzwe ogisijeni) igomba kuba hafi ya hydrogène ya hydrogène “yakira” (ubusanzwe azote ihambiriwe na hydrogène), birashobora kugorana cyane kubona ihuza aho abaterankunga hafi ya bose begereye abemera. Icya gatatu, hariho ingero nke zamahugurwa yuburyo bwubushakashatsi, birakenewe rero gusobanukirwa imikoranire ishobora kuba itatu-hagati ya aside amine hashingiwe kumurongo wa 1D ukoresheje amakuru ajyanye nubwihindurize bwa poroteyine zibishinzwe.

Fizika yakoreshejwe bwa mbere mu kwerekana imikoranire ya atome mu gushakisha ihinduka ryiza, kandi hashyizweho uburyo bwo guhanura imiterere ya poroteyine. Karplus, Levitt na Warshel bahawe igihembo cyitiriwe Nobel muri Chimie 2013 kubera ibikorwa byabo byo kubara poroteyine. Nyamara, uburyo bushingiye kuri fiziki buhenze kubarwa kandi busaba gutunganywa hafi, kubwibyo rero ibice bitatu-byuzuye ntibishobora guhanurwa. Ubundi buryo "bushingiye ku bumenyi" ni ugukoresha ububiko bwububiko buzwi nuburyo bukurikirana kugirango uhugure moderi ukoresheje ubwenge bwubukorikori no kwiga imashini (AI-ML). Hassabis na Jumper bakoresha ibintu byombi bya fiziki na AI-ML, ariko guhanga udushya no gusimbuka imikorere yuburyo bukomoka ahanini kuri AI-ML. Abashakashatsi bombi bahujije guhanga ububiko rusange rusange hamwe ninganda zo kubara-inganda zo gukora AlphaFold.

Tubwirwa n'iki ko "bakemuye" urujijo rwo guhanura? Mu 1994, hashyizweho amarushanwa ya Critical Assessment of Structure Prediction (CASP), ahura buri myaka ibiri kugirango akurikirane aho ubuhanuzi bugeze. Abashakashatsi bazagabana 1D ikurikirana ya poroteyine imiterere iherutse gukemura, ariko ibisubizo bikaba bitaratangazwa. Abahanuzi bahanura imiterere-yuburyo butatu bakoresheje uru rutonde rwa 1D, kandi uwasuzumye yigenga yigenga ubwiza bwibisubizo byavuzwe abigereranya nuburyo butatu butangwa nubushakashatsi (butangwa gusa kubisuzuma). CASP ikora isuzuma ryukuri rihumye kandi ikandika buri gihe imikorere isimbuka ijyanye no guhanga udushya. Mu nama ya 14 ya CASP mu 2020, ibisubizo byahanuwe na AlphaFold byagaragaje gusimbuka mu mikorere ku buryo abateguye batangaje ko ikibazo cyo guhanura imiterere ya 3D cyakemutse: ukuri kw'ibyahanuwe hafi ya byose byari hafi y'ibipimo by'ubushakashatsi.

Ubusobanuro bwagutse ni uko ibikorwa bya Hassabis na Jumper byerekana neza uburyo AI-ML ishobora guhindura siyanse. Ubushakashatsi bwayo bwerekana ko AI-ML ishobora kubaka hypothesse igoye ituruka kumasoko menshi yamakuru, ko uburyo bwo kwitondera (busa nubwa ChatGPT) bushobora kuvumbura ibintu byingenzi biterwa nisoko ryamakuru, kandi ko AI-ML ishobora kwisuzuma ubuziranenge bwibisubizo byatanzwe. AI-ML mubyukuri ikora siyanse.