Bekunokuthini ukuba besinokusebenzisa ubukrelekrele bokuzenzela ukuphendula enye yezona zinto zingaqondakaliyo ebomini – ukusonga iprotein? Izazinzulu bezisebenza kule nto kangangamashumi eminyaka.
Oomatshini ngoku banokuqikelela ubume beprotheyini ngokuchaneka okumangalisayo besebenzisa iimodeli zokufunda nzulu, ukuguqula uphuhliso lwamachiza, i-biotechnology, kunye nolwazi lwethu lweenkqubo ezisisiseko zebhayoloji.
Ndijoyine kuphononongo kwindawo enomdla ye-AI yeprotein esongelayo, apho itekhnoloji ye-cutting-edge ingqubana nobunzima bobomi ngokwabo.
Ukutyhila iMfihlakalo yokuSonga iProtein
Iiprotheyini zisebenza emizimbeni yethu njengoomatshini abancinci ukwenza imisebenzi ebalulekileyo njengokuqhekeza ukutya okanye ukuhambisa ioksijini. Kufuneka zisongwe ngokuchanekileyo ukuze zisebenze ngokufanelekileyo, kanye njengesitshixo kufuneka sisikwe ngokuchanekileyo ukuze singene kwisitshixo. Ngokukhawuleza ukuba iprotheni idalwe, inkqubo enzima kakhulu yokusonga iqala.
Ukusonga iprotein yinkqubo apho amatyathanga amade ee-amino acids, iibhloko zokwakha zeproteni, asonga abe ngamacala amathathu ayalela ukusebenza kweprotein.
Qwalasela umtya omde wamaso ekufuneka acwangciswe ngendlela echanekileyo; oku kwenzeka xa iprotein isonga. Ukanti, ngokungafaniyo namaso, iiamino acid zineempawu ezikhethekileyo yaye zisebenzisana ngeendlela ezahlukahlukeneyo, nto leyo eyenza ukusonga iprotini kube yinkqubo entsonkothileyo nebuthathaka.
Umfanekiso olapha umela i<em>hemoglobin yomntu, eyiproteni esongiweyo eyaziwayo
Iiprotheyini kufuneka zigobe ngokukhawuleza kwaye ngokuchanekileyo, okanye ziya kuba zingalunganga kwaye zineziphene. Oko kunokukhokelela kwizigulo ezifana ne-Alzheimer kunye ne-Parkinson. Ubushushu, uxinzelelo, kunye nobukho bezinye iimolekyuli ezikwiseli zonke zinempembelelo kwinkqubo yokusonga.
Emva kwamashumi eminyaka yophando, izazinzulu zisazama ukufumanisa indlela iiproteni ezisonga ngayo.
Ngombulelo, ukuqhubela phambili kubukrelekrele bokwenziwa kuphucula uphuhliso kwicandelo. Izazinzulu zinokuqikelela ukwakheka kweeproteni ngokuchanekileyo kunanini na ngaphambili ngokusebenzisa umatshini wokufunda iialgorithms ukuphonononga umthamo omkhulu wedatha.
Oku kunamandla okutshintsha uphuhliso lwamayeza kunye nokwandisa ulwazi lwethu lwemolekyuli yesigulo.
Ngaba Oomatshini Basebenza Ngcono?
Iindlela zokuSonga iiProtheyini eziqhelekileyo zineMida
Izazinzulu bezizama ukufumanisa ukusongwa kweeprotheyini amashumi eminyaka, kodwa ubucukubhede benkqubo buye benza lo mbandela waba ngumngeni.
Iindlela zoqikelelo lwesakhiwo seprotheyini eqhelekileyo zisebenzisa indibaniselwano yeendlela zovavanyo kunye nemodeli yekhompyuter, nangona kunjalo, ezi ndlela zonke zinemiqobo.
Ubuchule bokulinga obufana neX-reyi crystallography kunye nenyukliya magnetic resonance (NMR) inokutya ixesha kwaye ibize kakhulu. Kwaye, iimodeli zekhompyuter ngamanye amaxesha zithembele kwiingqikelelo ezilula, ezinokuthi zikhokelela ekuqikeleleni okungalunganga.
I-AI inokuyoyisa le Miqobo
Ngethamsanqa, kukubhadla okungeyonyani ibonelela ngesithembiso esitsha soqikelelo oluchanekileyo nolusebenzayo lwesakhiwo seprotheyini. Ii-algorithms zokufunda koomatshini zinokujonga umthamo omkhulu wedatha. Kwaye, batyhila iipatheni ezinokuthi abantu baziphose.
Oku kuye kwaphumela ekudalweni kwezixhobo zesoftware entsha kunye namaqonga akwaziyo ukuqikelela ubume beprotheyini ngokuchaneka okungalinganiyo.
Eyona ndlela ithembisayo yokuFunda ngoMatshini we-Algorithms yeProtein Structure Prediction
Inkqubo yeAlphaFold eyakhiwe nguGoogle DeepMind Iqela lelinye lenkqubela phambili ethembisayo kule ndawo. Ifumene inkqubela phambili enkulu kwiminyaka yakutshanje ngokusebenzisa ii-algorithms ezinzulu zokufunda ukuqikelela ukwakheka kweeproteni ngokusekelwe kulandelelwano lwazo lwe-amino acid.
Uthungelwano lwe-Neural, oomatshini be-vector abaxhasayo, kunye namahlathi angaqhelekanga aphakathi kwezinye iindlela zokufunda koomatshini ezibonisa isithembiso sokuqikelela ubume beprotheyini.
Ezi algorithms zinokufunda kwiiseti zedatha ezinkulu. Kwaye, banokulindela ulungelelwaniso phakathi kwee-amino acid ezahlukeneyo. Ngoko, makhe sibone ukuba isebenza njani.
Uhlalutyo lwe-Co-evolutionary kunye ne-First AlphaFold Generation
Impumelelo UAlFold yakhelwe kwimodeli yenethiwekhi ye-neural enzulu eyaphuhliswa kusetyenziswa uhlalutyo lwe-co-evolutionary. Ingcamango ye-co-evolution ithi ukuba i-amino acids ezimbini kwiprotheni zisebenzisana nomnye, ziya kuphuhlisa kunye ukuze zigcine ikhonkco yazo esebenzayo.
Abaphandi banokufumanisa ukuba zeziphi izibini ze-amino acid ezinokuthi ziqhagamshelane kwisakhiwo se-3D ngokuthelekisa ukulandelelana kwe-amino acid yeeprotheyini ezininzi ezifanayo.
Le datha isebenza njengesiseko sophindaphindo lokuqala lwe-AlphaFold. Iqikelela ubude phakathi kweeperi ze-amino acid kunye nee-engile ze-peptide bond ezizidibanisa. Le ndlela igqwesile zonke iindlela zangaphambili zokuqikelela ubume beprotheyini ukusuka kulandelelwano, nangona ukuchaneka kwakusathintelwe kwiiprotheni ezingenazo iitemplates ezibonakalayo.
I-AlphaFold yesi-2: Indlela entsha eNtsha
I-AlphaFold2 yinkqubo yekhompyutha eyenziwe yi-DeepMind esebenzisa ulandelelwano lwe-amino acid yeprotheni ukuqikelela ubume be-3D beprotheni.
Oku kubalulekile kuba ubume beprotheyini buchaza indlela esebenza ngayo, kwaye ukuqonda umsebenzi wayo kunokunceda izazinzulu ziphuhlise amayeza ajolise kwiprotheni.
Inethiwekhi ye-neural ye-AlphaFold2 ifumana njengegalelo ulandelelwano lwe-amino acid yeprotheni kunye neenkcukacha malunga nokuba olo landelelwano luthelekiseka njani nolunye ulandelelwano kuluhlu lwedatha (oku kubizwa ngokuba “lulungelelwaniso lolandelelwano”).
Inethiwekhi ye-neural yenza uqikelelo malunga nesakhiwo se-3D seprotheni esekelwe kweli galelo.
Yintoni eyahlulayo kwi-AlphaFold2?
Ngokuchaseneyo nezinye iindlela, i-AlphaFold2 iqikelela ukwakheka kwe-3D yokwenyani yeprotheyini kunokwahlukana nje phakathi kwezibini ze-amino acids okanye ii-engile phakathi kweebhondi ezizidibanisayo (njengoko kwenziwa i-algorithms yangaphambili).
Ukuze uthungelwano lwe-neural lulindele ulwakhiwo olupheleleyo ngexesha elinye, ulwakhiwo lufakwe ikhowudi ekupheleni ukuya ekupheleni.
Olunye uphawu oluphambili lwe-AlphaFold2 kukuba ibonelela ngoqikelelo lokuba izithembile kangakanani kuqikelelo lwayo. Oku kunikezelwa njengombala wekhowudi kwisakhiwo esilindelekileyo, kunye nobomvu obumele ukuzithemba okuphezulu kunye noluhlaza okwesibhakabhaka olubonisa ukuzithemba okuphantsi.
Oku kuluncedo kuba kwazisa izazinzulu malunga nokuzinza kokuqikelelwa.
Ukuqikelela uLwakhiwo oluDityanisiweyo lolandelelwano oluliqela
Ukwandiswa kwamva nje kwe-Alphafold2, eyaziwa ngokuba yi-Alphafold Multimer, iqikelela ulwakhiwo oludityanisiweyo lolandelelwano oluninzi. Isenamazinga aphezulu eempazamo nokuba iqhuba ngcono kakhulu kuneendlela zangaphambili. Kuphela i-% 25 ye-4500 yeeprotheyini eziyinkimbinkimbi ziqikelelwe ngempumelelo.
I-70% yemimandla enqabileyo yokubunjwa koqhagamshelwano yayiqikelelwe ngokuchanekileyo, kodwa ukuqhelaniswa okuhambelana neeprotheni ezimbini kwakungalunganga. Xa ubunzulu bolungelelwaniso oluphakathi bungaphantsi kwe-30 yolandelelwano, ukuchaneka koqikelelo lwe-Alphafold multimer kuncipha kakhulu.
Usetyenziswa njani Uqikelelo lweAlphafold
Imifuziselo eqikelelweyo esuka kwi-AlphaFold inikezelwa kwiifomathi zefayile ezifanayo kwaye ingasetyenziswa ngendlela efanayo nezakhiwo zovavanyo. Kubalulekile ukuthathela ingqalelo uqikelelo oluchanekileyo olunikezwa kunye nemodeli ukuze kuthintelwe ukungaqondani.
Iluncedo ngakumbi kwizakhiwo ezintsonkothileyo ezifana ne-homomers ephothiweyo okanye iiproteni ezigoqa kuphela xa kukho
i-ligand engaziwayo.
Eminye imingeni
Ingxaki ephambili ekusebenziseni izakhiwo eziqikelelweyo kukuqonda i-dynamics, i-ligand selectivity, ulawulo, i-allostery, utshintsho emva kokuguqulelwa, kunye ne-kinetics yokubopha ngaphandle kokufikelela kwiprotheni kunye nedatha ye-biophysical.
U kufunda kunye nophando lwe-molecular dynamics olusekwe kwifiziksi lunokusetyenziswa ukoyisa le ngxaki.
Olu phando lunokuxhamla kubungcali obukhethekileyo kunye nolwakhiwo lwekhompyutha olusebenzayo. Ngelixa i-AlphaFold iphumelele ukuqhubela phambili okukhulu ekucingeleni ubume beprotheyini, kusekho okuninzi ekufuneka kufundwe kwicandelo lebhayoloji yolwakhiwo, kwaye uqikelelo lwe-AlphaFold sisiqalo sofundo lwexesha elizayo.
Zeziphi Ezinye Izixhobo Eziphawulekayo?
I-RoseTTFold
I-RoseTTAFold, eyenziwe ngabaphandi beYunivesithi yaseWashington, ikwasebenzisa i-algorithms yokufunda enzulu ukuqikelela ubume beprotheyini, kodwa ikwadibanisa nendlela entsha eyaziwa ngokuba "yi-torsion angle dynamics simulations" ukuphucula izakhiwo eziqikelelweyo.
Le ndlela iye yavelisa iziphumo ezikhuthazayo kwaye inokuba luncedo ekoyiseni imida yezixhobo ezikhoyo zokugoqa iiprotheyini ze-AI.
iRosetta
Esinye isixhobo, i-trRosetta, iqikelela ukusongwa kweprotheyini ngokusebenzisa i-a inethiwekhi yomnatha baqeqeshwe kwizigidi zolandelelwano lweprotheyini kunye nezakhiwo.
Ikwasebenzisa "i-template-based modeling" ubuchule bokudala uqikelelo oluchanekileyo ngokuthelekisa iprotheni ekujoliswe kuyo kunye nezakhiwo ezaziwayo ezinokuthelekiswa.
Kubonakalisiwe ukuba i-trRosetta iyakwazi ukuqikelela ubume beeprotheyini ezincinci kunye neeprotheyini eziyinkimbinkimbi.
I-DeepMetaPSICOV
I-DeepMetaPSICOV sesinye isixhobo esigxile ekuqikeleleni iimephu zoqhagamshelwano lweprotheyini. Ezi, zisetyenziswa njengesikhokelo sokuqikelela ukusongwa kweeprotheyini. Isebenzisa ukufunda okunzulu iindlela zokuqikelela ukubakho konxibelelwano lwentsalela ngaphakathi kwiproteni.
Ezi kamva zisetyenziselwa ukuqikelela imephu yoqhagamshelwano iyonke. I-DeepMetaPSICOV ibonise amandla ekuqikeleleni izakhiwo zeprotheni ngokuchaneka okukhulu, nangona iindlela zangaphambili ziye zasilela.
Lisiphathele Ntoni Ikamva?
Ikamva lokusonga iprotein ye-AI liqaqambile. I-algorithms esekwe kufundo olunzulu, ngakumbi i-AlphaFold2, isandula ukwenza inkqubela phambili enkulu ekuqikeleleni ngokuthembekileyo ulwakhiwo lweprotheyini.
Oku kufunyanisiweyo kunamandla okuguqula uphuhliso lwamachiza ngokuvumela izazinzulu ukuba ziqonde ngcono ukwakheka kunye nomsebenzi weeprotheni, eziziithagethi eziqhelekileyo zonyango.
Nangona kunjalo, imiba efana noqikelelo lweprotein complexes kunye nokufumana imeko yokwenyani yokusebenza kwezakhiwo ezilindelweyo ihleli. Uphando oluthe kratya luyafuneka ukusombulula le miba kunye nokwandisa ukuchaneka kunye nokuthembeka kwe-AI yeprotheyini yokugoqa i-algorithms.
Ukanti, iingenelo ezinokubakho kobu bugcisa bukhulu kakhulu, kwaye bunamandla okukhokelela ekuvelisweni kwamayeza asebenza ngakumbi nachanekileyo.
Shiya iMpendulo