Ososayensi bembula izakhiwo ezifihliwe zezinto zokwakha nama-biomolecules besebenzisa icrystallography kanye ne-cryo-electron microscopy (cryo-EM). Kodwa-ke, njengoba lezi ziqondiso zibhekana nezinkinga ezikhula njalo, ukufunda ngomshini sekuphenduke umsizi obalulekile.
Kulokhu okuthunyelwe, sizobheka ukuhlangana okuthakazelisayo "Kwezindlela Zokufunda Ngomshini ze-Crystallography ne-Cryo-EM." Hlanganyela nathi njengoba siphenya umthelela oguquguqukayo wobuhlakani bokwenziwa ekuvuleni izimfihlo zendawo yonke ye-athomu namangqamuzana.
Okokuqala, ngifuna ukungena esihlokweni futhi ngisho ukuthi iyini ngempela imigomo ye-crystallography kanye ne-Cryo-Em, sizobe siphenya ngokuqhubekayo lapho. ukufunda imishini angene emdlalweni.
I-Crystallography
I-Crystallography wucwaningo lokuhlelwa kwama-athomu ezintweni ezicwebezelayo. Amakristalu ayizinto eziqinile ezakhiwe ngama-athomu ahlelwe ngephethini ephindaphindayo ukuze akhe isakhiwo esakheke kakhulu.
Ngenxa yalokhu kuhlelwa njalo, izinto zokwakha zinezakhiwo nokuziphatha okuhlukile, okwenza icrystallography ibaluleke ekuqondeni izakhiwo zezinto eziningi.
Ososayensi bangahlola i-crystal lattice besebenzisa amasu afana ne-X-ray diffraction, banikeze ulwazi olubalulekile ngokuma kwe-athomu nokusebenzisana kwebhondi. I-Crystallography ibalulekile emikhakheni eminingi, kusukela kusayensi yezinto zokwakha kanye nekhemistri kuya ku-geology kanye ne-biology. Kuyasiza ekuthuthukiseni izinto ezintsha kanye nokuqonda izakhiwo zamaminerali.
Ingasisiza ngisho nasekuqondeni izakhi eziyinkimbinkimbi zamangqamuzana ezinto eziphilayo njengamaprotheni.
I-Cryo-EM (Cryo-Electron Microscopy)
I-Cryo-electron microscopy (i-Cryo-EM) iwubuchwepheshe bokucabanga obuyindida obuvumela abacwaningi ukuthi babone izakhiwo ezinezinhlangothi ezintathu zama-biomolecules ngokulungiswa kwe-athomu noma eduze kwe-athomu.
I-Cryo-EM ilondoloza ama-biomolecules esimweni sawo esiseduze nesemvelo ngokuwaqanda ngokushesha ku-nitrogen ewuketshezi, ngokuphambene ne-electron microscopy evamile, edinga amasampuli ukuthi alungiswe, angcoliswe, futhi aphelelwe amanzi.
Lokhu kuvimbela ukwakheka kwekristalu yeqhwa, kulondoloze ukwakheka kwezinto eziphilayo. Ososayensi manje bangabona imininingwane enembayo yezakhiwo ezinkulu zamaphrotheni, amagciwane, nama-organelles amaselula, okuhlinzeka ngemininingwane ebalulekile ngemisebenzi yabo kanye nobudlelwano.
I-Cryo-EM iguqule i-structural biology ngokuvumela abacwaningi ukuthi bahlole izinqubo zebhayoloji emazingeni emininingwane ayengacatshangwa ngaphambili. Izicelo zayo zisukela ekutholakaleni kwezidakamizwa nasekuthuthukisweni komgomo kuya ekuqondeni izisekelo zamangqamuzana okugula.
Kungani Zibalulekile?
I-Cryo-EM kanye ne-crystallography kubalulekile ekuthuthukiseni ukuqonda kwethu umhlaba wemvelo.
I-Crystallography isenza sikwazi ukuthola futhi siqonde ukuhlelwa kwe-athomu ezintweni zokwakha, kusivumela ukuthi sakhe izinhlanganisela zenoveli ezinezimfanelo ezithile zokusetshenziswa okubanzi. I-Crystallography ibalulekile ekulolongeni isiko lethu lesimanje, kusukela kuma-semiconductors asetshenziswa ku-electronics kuya emithini esetshenziselwa ukwelapha izifo.
Ngakolunye uhlangothi, i-Cryo-EM inikeza umbono othakazelisayo wendlela yokuphila eyinkimbinkimbi. Ososayensi bathola ukuqonda ngezinqubo ezibalulekile zebhayoloji ngokubuka ukwakheka kwama-biomolecules, okubavumela ukuthi bakhiqize imithi engcono, baklame izindlela zokwelapha eziqondiswe kubo, futhi balwe ngokuphumelelayo nezifo ezithathelwanayo.
Intuthuko ye-Cryo-EM ivula imibono emisha kwezokwelapha, i-biotechnology, kanye nokuqonda kwethu konke okubalulekile kwempilo.
Ukuthuthukisa Ukubikezela Kwesakhiwo Nokuhlaziya Ngokufunda Ngomshini ku-Crystallography
Ukufunda ngomshini kube usizo ngendlela emangalisayo ku-crystallography, kushintsha indlela ososayensi ababikezela futhi bahumushe ngayo izakhiwo zekristalu.
Ama-algorithms angakwazi ukukhipha amaphethini nokuhlotshaniswa kusuka kudathasethi enkulukazi yezinhlaka zekristalu ezaziwayo, okuvumela ukubikezela okusheshayo kwezakhiwo zekristalu ezintsha ezinembayo ezingenakuqhathaniswa.
Isibonelo, abacwaningi be-Thorn Lab bafakazele ukuphumelela kokufunda komshini ekubikezeleni ukuzinza kwekristalu namandla okwakheka, okuhlinzeka ngemininingwane ebalulekile kuzakhiwo ze-thermodynamic zezinto zokwakha.
Lokhu kuthuthukiswa akusheshisi kuphela ukutholakala kwezinto ezintsha kodwa futhi nokwenza kahle kwamanje, kuletha inkathi entsha yocwaningo lwempahla enezimfanelo ezingcono nokusebenza.
Isithombe: Isibonelo sesakhiwo sekristalu esiboniswe kusofthiwe ye-Mercury.
Ukufunda Ngomshini Kwembula Kanjani I-Cryo-EM?
Ukufunda ngomshini kuvule umhlaba omusha wamathuba ku-cryo-electron microscopy (Cryo-EM), okuvumela ososayensi ukuthi bajule ekujuleni kobunzima besakhiwo sama-biomolecules.
Abacwaningi bangahlaziya amanani amakhulu wedatha ye-cryo-EM besebenzisa ubuchwepheshe obunoveli obufana ukufunda okujulile, yakha kabusha amamodeli anezinhlangothi ezintathu zamangqamuzana ebhayoloji ngokucacile okungenakuqhathaniswa nokunemba.
Le nhlanganisela yokufunda komshini nge-cryo-EM ivumele ukucatshangwa kwezakhiwo zamaphrotheni ebezingachazeki ngaphambilini, okuhlinzeka ngemininingwane emisha emisebenzini yabo nobudlelwano.
Inhlanganisela yalobu buchwepheshe inesithembiso esikhulu sokutholwa kwezidakamizwa njengoba ivumela abacwaningi ukuthi baqondise ngokunembile amasayithi athile abophayo, okuholela ekudalweni kwemithi esebenza ngempumelelo kakhulu yezinkinga ezihlukahlukene.
Ama-Algorithms Wokufunda Ngomshini Wokusheshisa Ukuhlaziywa Kwedatha ye-Cryo-EM
Uphenyo lwe-Cryo-EM lukhiqiza idathasethi enemininingwane nenkulu, okungaba kokubili isipho nesiqalekiso kubacwaningi. Kodwa-ke, izindlela zokufunda zomshini zibonise ukuthi zibalulekile ekuhlaziyeni okusebenzayo nasekuchazeni idatha ye-cryo-EM.
Ososayensi bangasebenzisa izindlela zokufunda ezingagadiwe ukuze bathole ngokuzenzakalelayo futhi bahlukanise izakhiwo zamaphrotheni ezihlukahlukene, behlise ukusebenza kwezandla okuthatha isikhathi.
Le ndlela ayisheshi nje kuphela ukuhlaziywa kwedatha kodwa futhi ithuthukisa ukwethembeka kokutholiwe ngokususa ukuchema kwabantu ekuchazeni idatha yesakhiwo eyinkimbinkimbi.
Ukufakwa komshini wokufunda ekuhlaziyweni kwedatha ye-Cryo-EM, njengoba kuboniswe emisebenzini yakamuva, kunikeza indlela yolwazi olujulile lwezinqubo zebhayoloji eziyinkimbinkimbi kanye nokuhlolwa okuphelele kakhulu kwemishini yamangqamuzana okuphila.
Ngaphakathi Kwezindlela Ezihlanganisiwe: Ukuvala Igebe Lokulinga-Computation
Ukufunda ngomshini kunamandla okuvala igebe phakathi kwedatha yokuhlola namamodeli ekhompyutha ku-crystallography ne-cryo-EM.
Ukuhlanganiswa kwedatha yokuhlola nezindlela zokufunda zomshini kunika amandla ukuthuthukiswa kwamamodeli abikezelayo anembile, ukuthuthukisa ukwethembeka kokunqunywa kwesakhiwo kanye nesilinganiso sendawo.
Ukudlulisa ukufunda, indlela esebenzisa ulwazi olufundwe endaweni eyodwa kuya kwenye, ibonakala njengethuluzi elibalulekile lokuthuthukisa ukusebenza kahle kophenyo lwe-crystallographic nolwe-Cryo-EM kulo mongo.
Amasu amaHybrid, ahlanganisa imininingwane yokuhlola namandla ekhompiyutha, amele inketho ephambili yokuxazulula izinselele zesayensi eziyinselele, ezithembisa ukuguqula indlela esibona ngayo kanye nokukhohlisa umhlaba we-athomu ne-molecule.
Ukusebenzisa Amanethiwekhi E-Convolutional Neural Ukukhetha Izinhlayiya ku-Cryo-EM
Ngokunikeza izithombe ezinokulungiswa okuphezulu kwama-molecule ezinto eziphilayo, i-cryo-electron microscopy (Cryo-EM) iguqule ukucwaninga kwezakhiwo zama-macromolecular.
Nokho, ukucosha izinhlayiyana, okuhlanganisa ukuqaphela nokukhipha izithombe zezinhlayiyana ngazinye kuma-micrographs e-Cryo-EM, kube umsebenzi odla isikhathi nonzima.
Abacwaningi benze inqubekelaphambili enkulu ekwenzeni le nqubo ngokuzenzakalelayo ngokusetshenziswa komshini wokufunda, ikakhulukazi amanethiwekhi we-convolutional neural (ama-CNN).
I-DeepPicker ne-Topaz-Denoise zimbili ubuchule bokufunda obujulile enika amandla ukukhethwa kwezinhlayiyana okuzenzakalelayo ngokugcwele ku-cryo-EM, kusheshisa kakhulu ukucutshungulwa nokuhlaziywa kwedatha.
Izindlela ezisekelwe ku-CNN sezibucayi ekusheshiseni izinqubo ze-Cryo-EM futhi zivumela abacwaningi ukuthi bagxile ekuphenyweni kwezinga eliphezulu ngokuthola ngokunembile izinhlayiya ngokunemba okuphezulu.
Ukuthuthukiswa Kwe-Crystallography Ngokusebenzisa Ukumodela Okuqagelayo
Ikhwalithi yedatha ye-diffraction kanye nemiphumela ye-crystallization ingaba nomthelela omkhulu ekunqunyweni kwesakhiwo ku-macromolecular crystallography.
Amanethiwekhi e-Artificial neural (ANNs) nemishini yokusekela i-vector (ama-SVM) asetshenziswe ngempumelelo ukuze kuthuthukiswe izilungiselelo zokucwebezela kanye nesibikezelo sekhwalithi yokuhluka kwekristalu. Amamodeli aqagelayo akhiqizwa abacwaningi asiza ekwakhiweni kokuhlolwa futhi athuthukise izinga lempumelelo yokuhlolwa kwekristalu.
Lawa mamodeli angakwazi ukwembula amaphethini aholela emiphumeleni emihle ngokuhlola umthamo omkhulu wedatha ye-crystallization, asize abacwaningi ekukhiqizeni amakristalu ekhwalithi ephezulu okuhlolwa kwe-X-ray diffraction okulandelayo. Ngenxa yalokho, ukufunda ngomshini sekuphenduke ithuluzi elibalulekile lokuhlola i-crystallographic okusheshayo nokuhlosiwe.
Ukuthuthukisa Ukuqashelwa Kwesakhiwo se-Cryo-EM
Ukuqonda ukwakheka kwesibili kwama-molecule ebhayoloji kusetshenziswa amamephu wokuminyana we-Cryo-EM kubalulekile ekunqumeni imisebenzi yawo nokusebenzisana kwawo.
Izindlela zokufunda ngomshini, okuyizakhiwo zokufunda ezijulile ezifana namanethiwekhi okuguqulwayo namanethiwekhi aphindelelayo, zisetshenziselwe ukuthola izici zesakhiwo sesibili kumamephu we-cryo-EM ngokuzenzakalela.
Lezi zindlela ziphenya izici zasendaweni kumamephu wokuminyana, okuvumela ukuhlukaniswa okunembile kwezinto zesakhiwo sesibili. Ukufunda ngomshini kuvumela abacwaningi ukuthi baphenye izakhiwo zamakhemikhali eziyinkimbinkimbi futhi bathole imininingwane ngemisebenzi yabo yebhayoloji ngokwenza le nqubo edinga abasebenzi abaningi ibe ngokuzenzakalela.
Isithombe: Ukwakhiwa kabusha kwe-Cryo-EM kwesakhiwo
Ukwakhiwa Kwemodeli Ye-Crystallography kanye Nokusheshisa Ukuqinisekisa
Ukwakhiwa kwemodeli nokuqinisekiswa yizigaba ezibalulekile ku-macromolecular crystallography ukuze kuqinisekiswe ukunemba kwemodeli yesakhiwo nokwethembeka.
Ubuchwepheshe bokufunda komshini obufana nama-convolutional autoencoder namamodeli e-Bayesian asetshenziselwe ukusiza nokuthuthukisa lezi zinqubo. I-AAnchor, isibonelo, isebenzisa ama-CNN ukuze ibone ama-amino acids kumamephu wokuminyana we-Cryo-EM, esiza ekuthuthukisweni kwemodeli okuzenzakalelayo.
Amamodeli wokufunda womshini wase-Bayesian nawo asetshenziswa ukuhlanganisa idatha yokuhluka kwe-X-ray nokwabela amaqembu esikhala kumamephu amancane we-electron density.
Le ntuthuko ayisheshi nje kuphela ukunqunywa kwesakhiwo kodwa ihlinzeka nokuhlola okunabile kwekhwalithi yamamodeli, okuholela emiphumeleni yocwaningo eqinile nengaphinde ikhiqizeke.
Ikusasa Lokufunda Ngomshini ku-Structural Biology
Njengoba kubonakala ngenani elikhulayo lokushicilelwa kwesayensi, ukuhlanganiswa kokufunda komshini ku-cryo-EM kanye ne-crystallography kuthuthukiswa njalo, kuhlinzeka ngobuningi bezixazululo zenoveli nezinhlelo zokusebenza.
Ukufunda ngomshini kuthembisa ukuqhubeka nokuguqula indawo yebhayoloji yesakhiwo ngokuthuthukiswa okuqhubekayo kwama-algorithms anamandla kanye nokwandiswa kwezinsiza ezikhethiwe.
Ukusebenzisana phakathi kokufunda komshini kanye nebhayoloji yesakhiwo kuvula indlela yokutholwa kanye nemininingwane emhlabeni we-athomu namamolekyuli, kusukela ekunqumeni kwesakhiwo esisheshayo kuya ekutholweni kwezidakamizwa nobunjiniyela bamaprotheni.
Ucwaningo oluqhubekayo ngalesi sihloko esithakazelisayo lukhuthaza ososayensi ukuthi basebenzise amandla e-AI futhi bavule izimfihlakalo zamabhulokhi okwakha empilo.
Isiphetho
Ukufakwa kobuchwepheshe bokufunda komshini ku-crystallography kanye ne-cryo-electron microscopy kuvule inkathi entsha kubhayoloji yesakhiwo.
Ukufunda ngomshini kusheshise kakhulu isivinini socwaningo futhi kwaletha imininingwane engenakuqhathaniswa emhlabeni we-athomu namangqamuzana, kusukela ekuzisebenzeleni okunzima okunjengokukhethwa kwezinhlayiyana kuya ekuthuthukiseni ukumodela okubikezelwayo kokucwebezela kanye nekhwalithi yokuhlukanisa.
Abacwaningi manje sebengakwazi ukuhlola ngempumelelo imiqulu emikhulu yedatha besebenzisa i-convolutional amanethiwekhi we-neural kanye namanye ama-algorithms athuthukisiwe, alindele ngokushesha izakhiwo zekristalu futhi akhiphe ulwazi olubalulekile kumamephu wokuminyana kwe-cryo-electron microscopy.
Le ntuthuko ayisheshi nje kuphela ukusebenza kokuhlolwa kodwa futhi ivumela ukucwaninga okujulile kwezakhiwo nemisebenzi yebhayoloji.
Ekugcineni, ukuhlangana kokufunda komshini kanye nebhayoloji yesakhiwo kushintsha indawo ye-crystallography kanye ne-cryo-electron microscopy.
Ngokuhlangene, lobu buchwepheshe obuphambili busisondeza ekuqondeni kangcono umhlaba we-athomu namamolekyuli, okuthembisa impumelelo eshintsha umdlalo ocwaningweni lwempahla, ukuthuthukiswa kwemithi, kanye nemishini eyinkimbinkimbi yokuphila ngokwayo.
Njengoba samukela lo mngcele omusha othakazelisayo, ikusasa lebhayoloji yesakhiwo likhanya ngokukhazimulayo ngamathuba angenamkhawulo kanye nekhono lokuxazulula izindida zemvelo ezinzima kakhulu.
shiya impendulo