TORA
Imwe nzira itsva yehunyanzvi yakagadziridzwa nechikwata chesainzi kuCentre for Genomic Regulation (CRG) muBarcelona yakawana kuvepo kweakawanda e 'remote control' ayo anodzora kushanda kwemapuroteni uye anogona kushandiswa sezvinangwa zvekuwana mishonga inoshanda. uye inoshanda mune dzakasiyana siyana pathologies senge dementia, cancer uye hutachiona hwehutachiona.
Aya 'remote controls' anozivikanwa nesainzi seallosteric saiti. Aya ndiwo masimba ari kure ari kure nenzvimbo yekuita kweprotein, asi ane hunyanzvi hwekuidzora kana kuigadzirisa", Júlia Domingo, wekutanga munyori-munyori wechidzidzo ichi, chakaburitswa neChitatu chino mumagazini "Nature". akatsanangurira ABC. Uye anowedzera fananidzo: "Zvinoita sekunge neiyo remote control unogona kubatidza nekudzima girobhu kana kudzora kusimba kwechiedza."
Muchiitiko ichi apo inotarisira kuvhara kana kugadzirisa basa remapuroteni anochengetedza basa ravo rakashandurwa muhusungwa. Semuenzaniso, kana iri cancer, mapuroteni akawana shanduko ane mashandiro adzo anoshandurwa, anozviita zvisina kujairika uye sero rinokura nenzira isina kujairika. Muzviitiko zvakawanda, hapana mishonga inogona kuenzanisa kana kuvhara chiitiko ichi chisina kujairika kana, kana iripo, haina kujeka uye inoburitswa kubva kune mamwe mapuroteni anoshanda zvakajairika.
Sechinyakare, vavhimi vezvinodhaka vakagadzira marapirwo anonangana nenzvimbo inoshanda yeprotein, ine dunhu diki rinoburitsa maitiro emakemikari apo zvinonangwa zvinosunga. Kukanganisa kwemishonga iyi, inozivikanwa semishonga ye orthosteric, ndeyokuti nzvimbo dzinoshanda dzemapuroteni akawanda dzakanyanya kufanana uye mishonga yakasunga uye yakadzivisa mapuroteni akawanda akasiyana panguva imwe chete, kunyange iyo inoshanda zvakajairika uye isingafadzi kubata, iyo. zvinogona kukonzera maside effects.
“Ikoko akapinda pfungwa ye<em>allosteria uye kugona kwainako kugadzira mishonga. Chinhu chinonakidza nezve allosteric masaiti ndechekuti iwo akanyanya kujeka kune yega puroteni. Kana aya masaiti eallosteric akawana chikamu cheprotein kumusoro uko mushonga unogona kumhara, ichave yakanyatso kurongeka kune iyo protein. Tichakwanisa kushuvira kuwana mishonga inoshanda,” anodaro muongorori.
“Hatisi kungoona kuti nzvimbo dzekurapa idzi dzakawanda, asi kune humbowo hwekuti dzinogona kushandiswa nenzira dzakasiyana. Panzvimbo pekungobatidza nekudzima, isu tinokwanisa kumisa chiitiko chavo senge thermostat. Kubva pamaonero einjiniya, zvinoita sekunge tarova goridhe, nekuti zvinotipa nzvimbo yakawanda yekugadzira 'smart zvinodhaka' zvinoenda kune zvakaipa uye kusvetuka zvakanaka", anotsanangura André Faure, postdoctoral muongorori kuCRG. uye wekutanga mubatanidzwa - munyori wechinyorwa.
matatu-dimensional mufananidzo unoratidza puroteni yemunhu PSD95-PDZ3 kubva kwakasiyana maonero. Morekuru inoratidzwa ichisunga kune inoshanda saiti yero. Bhuruu kusvika kune dzvuku ruvara gradient inoratidza inokwanisika allosteric nzvimbo - André Faure/ChimeraX
Nokuda kwekuwanikwa uku, boka racho rakashandisa nzira inovabvumira kutora mapuroteni uye maitiro ehurongwa uye kusangana kwepasi rose nemasayiti ose. Kuti vaite izvi, vakasarudza mapuroteni maviri akawandisa muproteome yedu yevanhu. "50% yeprotein yepamusoro ine allosteric kugona. Nzira yedu inoita kuti zvikwanisike kugadzira maatlasi enzvimbo dzeallosteric, izvo zvingaita kuti nzira yekutsvaga mishonga inoshanda zvakanyanya ”, anovimbisa Júlia Domingo.
Vanyori vekudzidza vakagadzira nzira inonzi kaviri-yakadzika PCA (ddPCA), iyo yavanotsanangura se "brute force experiment." "Tinotyora zvinhu nemaune muzviuru zvenzira dzakasiyana dzekugadzira mufananidzo wakakwana wekuti chimwe chinhu chinoshanda sei," anotsanangura kudaro ICREA Research Purofesa Ben Lehner, Coordinator weSystems Biology chirongwa kuCRG uye munyori wechidzidzo ichi. “Zvakafanana kana uchifungidzira kuti spark plug yakashata, asi pane kuti ungotarisa izvozvo, makanika anotsemura motokari yose otarisa maparts ose chimwe nechimwe. Nekuongorora zviuru gumi zvinhu panguva imwe chete, tinoona zvidimbu zvese zvakakosha. "
Tevere, isu tinoshandisa artificial intelligence algorithms kududzira mhedzisiro yelab.
Imwe yemabhenefiti makuru eiyo nzira, pamusoro pekurerutsa maitiro anodiwa ekutsvaga allosteric nzvimbo, inzira inokwanisika uye inosvikika kune chero marabhoritari ekutsvagisa munyika. "Zvinongoda kuwanikwa kune zvakakosha mamolecular biology reagents, kuwana DNA sequencer uye komputa. Nezvikamu zvitatu izvi, chero laboratori mumwedzi 2-3, ine bhajeti diki, inogona kuita iyi kuyedza paprotein yekufarira yavanoda ", anovimbisa Júlia Domingo. Tariro yevatsvaguri ndeyekuti masayendisiti edu achashandisa hunyanzvi uhu nekukurumidza uye zvizere mepu nzvimbo dzeallosteric dzemapuroteni evanhu rimwe nerimwe. “Kana isu tiine data rakakwana pamwe rimwe zuva tinogona kuenda nhanho imwe mberi uye kufanotaura kubva pakutevedzana kweprotein kusvika pakushanda. Shandisa idzi data kuti uvatungamirire senzira dzekurapa dziri nani kufanotaura kana imwe shanduko muprotein ichizoderera kuita chirwere ”, akapedzisa muongorori.
