KOKOA
Ua ʻike ʻia kahi ʻenehana hou i hoʻomohala ʻia e kahi hui ʻepekema ma ka Center for Genomic Regulation (CRG) ma Barcelona i ka nui o nā 'mana mamao' e hoʻomalu i ka hana o nā protein a hiki ke hoʻohana ʻia i mau pahuhopu e hoʻokō ai i nā lāʻau lapaʻau ʻoi aku ka maikaʻi. a maikaʻi hoʻi i nā maʻi maʻi like ʻole e like me ka dementia, ke kanesa a me nā maʻi ʻeha.
Ua ʻike ʻia kēia mau 'mana mamao' ma ke ʻano ʻepekema he paena allosteric. ʻO kēia nā mana mamao mamao loa mai ka pūnaewele o ka hana o ka protein, akā hiki ke hoʻoponopono a hoʻololi paha iā ia", ʻo Júlia Domingo, ka mea kākau mua o ka noiʻi, i paʻi ʻia i kēia Pōʻakolu ma ka puke pai "Nature", wehewehe iā ABC. A ua hoʻohui ʻo ia i kahi hoʻohālikelike: "Me he mea lā me kēlā mana mamao hiki iā ʻoe ke hoʻohuli i ka ʻōpuʻu kukui a hoʻopau a hoʻoponopono paha i ka ikaika o ke kukui."
I kēia hihia kahi i manaʻo ai e ālai a hoʻoponopono i ka hana o nā protein e mālama i kā lākou hana i hoʻololi ʻia i loko o ka hoʻopaʻa ʻana. No ka laʻana, i ka hihia o ka maʻi kanesa, ua hoʻololi ʻia ka hana o nā protein i loaʻa i ka mutation, hana ʻino lākou a ulu ʻole ke kelepona. I nā manawa he nui, ʻaʻohe lāʻau lapaʻau e hiki ke hoʻololi a hoʻopaʻa i kēia hana ʻino a i ʻole, inā loaʻa, ʻaʻole lākou kikoʻī a hoʻokuʻu pū ʻia mai nā protein ʻē aʻe e hana maʻamau.
ʻO ka mea maʻamau, ua hoʻolālā ka poʻe hahai lāʻau lapaʻau i nā lāʻau lapaʻau e kālele ana i ka pūnaewele ikaika o kahi protein, nona ka wahi liʻiliʻi e hoʻopuka i nā hopena kemika kahi e hoʻopaʻa ai nā pahu hopu. ʻO ka drawback o kēia mau lāʻau lapaʻau, i kapa ʻia ʻo nā lāʻau orthosteric, ʻo ia nā wahi hana o nā protein he nui like loa a ua hoʻopaʻa ʻia nā lāʻau lapaʻau a hoʻopaʻa i nā protein like ʻole i ka manawa like, ʻo ia hoʻi nā mea e hana maʻamau a ʻaʻole hoihoi i ka hoʻopā ʻana. hiki ke hana i nā hopena ʻaoʻao.
"Ma laila ʻo ia i komo ai i ka manaʻo o allosteria a me ka hiki ke hoʻolālā i nā lāʻau lapaʻau. ʻO ka mea hoihoi e pili ana i nā pūnaewele allosteric ʻo ia ka mea kikoʻī loa no kēlā me kēia protein. Inā loaʻa i kēia mau wahi allosteric kahi ʻāpana o ka ʻili protein kahi e pae ai ka lāʻau lapaʻau, e kikoʻī loa ia no kēlā protein. Hiki iā mākou ke makemake i nā lāʻau lapaʻau maikaʻi loa", wahi a ka mea noiʻi.
"ʻAʻole wale mākou e ʻike i ka nui o kēia mau pūnaewele therapeutic, akā aia nā hōʻike e hiki ke hoʻohana ʻia i nā ʻano like ʻole. Ma kahi o ka hoʻohuli ʻana iā lākou a hoʻopau, hiki iā mākou ke hoʻololi i kā lākou hana e like me ka thermostat. Mai ka ʻike ʻenehana, me he mea lā ua paʻi mākou i ke gula, no ka mea, hāʻawi ia iā mākou i ka nui o ka lumi e hoʻolālā ai i nā 'lāʻau lapaʻau akamai' e hele i ka maikaʻi a lele i ka maikaʻi", wehewehe ʻo André Faure, ka mea noiʻi postdoctoral ma CRG. a me ka mea kākau mua o ka ʻatikala.
kiʻi ʻekolu-dimensional e hōʻike ana i ka protein kanaka PSD95-PDZ3 mai nā manaʻo like ʻole. Hōʻike ʻia kahi mole e hoʻopaʻa ʻia i ka pae hana i ka melemele. Hōʻike ka gradient kala ʻulaʻula i nā pae allosteric hiki - André Faure/ChimeraX
No kēia ʻike, ua hoʻohana ka hui i kahi ala e hiki ai iā lākou ke lawe i kahi protein a me kahi ʻano ʻōnaehana a me kahi hālāwai honua me nā pūnaewele āpau. No ka hana ʻana i kēia, ua koho lākou i ʻelua mau protein nui loa i kā mākou proteome kanaka. "He 50% o ka ʻili protein i loaʻa ka mana allosteric. ʻO kā mākou ala e hiki ai ke hana i kahi atlas o nā pūnaewele allosteric, kahi e ʻoi aku ka maikaʻi o ka ʻimi ʻana i nā lāʻau lapaʻau maikaʻi", wahi a Júlia Domingo.
Ua hoʻomohala nā mea kākau noiʻi i kahi ʻenehana i kapa ʻia ʻo PCA hohonu ʻelua (ddPCA), a lākou e wehewehe nei he "hoʻokolohua hoʻoikaika ikaika." "Hoʻokaʻawale mākou i nā mea i nā tausani o nā ala like ʻole e hana i kahi kiʻi piha o ka hana ʻana o kekahi mea," wehewehe ʻo ICREA Research Professor Ben Lehner, Coordinator of the Systems Biology program ma CRG a me kahi mea kākau o ka noiʻi. “Me he mea lā inā manaʻo ʻoe he ʻino ka pahu ahi, akā ma kahi o ka nānā wale ʻana i kēlā, na ka mīkini e wehe i ke kaʻa holoʻokoʻa a nānā i nā ʻāpana āpau. Ma ka nānā ʻana i nā mea he ʻumi tausani i ka manawa hoʻokahi, ʻike mākou i nā ʻāpana āpau i koʻikoʻi loa. "
A laila, hoʻohana mākou i nā algorithm artificial intelligence e wehewehe i nā hopena lab.
ʻO kekahi o nā pōmaikaʻi nui o ke ʻano, ʻo ka hoʻohui ʻana i ka hoʻomaʻamaʻa ʻana i ke kaʻina hana e pono ai ka loaʻa ʻana o nā kahua allosteric, ʻo ia ka ʻenehana kūpono a hiki ke loaʻa no nā keʻena noiʻi ma ka honua. "Pono ia i ke komo ʻana i nā molecular biology reagents, ke komo ʻana i kahi sequencer DNA a me kahi kamepiula. Me kēia mau ʻāpana ʻekolu, hiki i kēlā me kēia keʻena hana i loko o 2-3 mau mahina, me kahi kālā liʻiliʻi, hiki ke hoʻokō i kēia hoʻokolohua ma ka protein o ka hoihoi a lākou e makemake ai", hōʻoia ʻo Júlia Domingo. ʻO ka manaʻolana o ka poʻe noiʻi e hoʻohana kā mākou poʻe ʻepekema i ka ʻenehana e hoʻopaʻa paʻa i nā pae allosteric o nā protein kanaka. "Inā lawa kā mākou ʻikepili i kekahi lā hiki iā mākou ke hele i hoʻokahi ʻanuʻu a wānana mai ke kaʻina protein e hana. E hoʻohana i kēia mau ʻikepili e alakaʻi iā lākou e like me nā lāʻau lapaʻau ʻoi aku ka maikaʻi e wānana inā e hoʻololi ʻia kahi hoʻololi i loko o kahi protein i kahi maʻi", i hoʻopau ai ka mea noiʻi.
