He aha inā hiki iā mākou ke hoʻohana i ka naʻauao hana e pane ai i kekahi o nā mea pohihihi nui o ke ola - ʻo ka pale ʻana i ka protein? Ua hana nā ʻepekema i kēia no nā makahiki he mau makahiki.
Hiki i nā mīkini i kēia manawa ke wānana i nā hana protein me ka pololei kupaianaha me ka hoʻohana ʻana i nā kumu hoʻonaʻauao hohonu, hoʻololi i ka hoʻomohala ʻana i ka lāʻau lapaʻau, biotechnology, a me kā mākou ʻike i nā kaʻina hana koʻikoʻi.
E hui pū me aʻu i ka ʻimi ʻana i ke aupuni hoihoi o AI protein folding, kahi e hui ai ka ʻenehana ʻokiʻoki me ka paʻakikī o ke ola ponoʻī.
Wehewehe ana i ka mea pohihihi o ka Pepa Polokina
Hana nā protein i loko o ko mākou kino e like me nā mīkini liʻiliʻi e hana i nā hana koʻikoʻi e like me ka wāwahi ʻana i ka meaʻai a i ʻole ka lawe ʻana i ka oxygen. Pono e pelu pono ia i mea e hana pono ai, e like me ke oki pono ia o ke ki a komo iloko o ka laka. Ke hana ʻia ka protein, hoʻomaka kahi kaʻina hana paʻakikī loa.
ʻO ka pelu ʻana i ka protein ke kaʻina hana e hoʻopili ai i nā kaulahao lōʻihi o nā waikawa amino, nā poloka kūkulu hale o ka protein, i loko o nā hale ʻekolu-dimensional e kuhikuhi i ka hana o ka protein.
E noʻonoʻo i kahi kaula lōʻihi o nā lei e pono ke kauoha ʻia i kahi ʻano pololei; ʻO kēia ka mea e hana ai i ka wā e pelu ai kahi protein. Akā naʻe, ʻaʻole e like me nā peʻa, he ʻano kūʻokoʻa ko nā amino acids a pili pū kekahi me kekahi ma nā ʻano like ʻole, e hana ana i ka hoʻopili ʻana i ka protein i mea paʻakikī a paʻakikī.
Hōʻike ke kiʻi ma ʻaneʻi i ka hemoglobin kanaka, ʻo ia ka protein i pelu ʻia
Pono e pelu koke nā protein a me ka pololei, a i ʻole e lilo lākou i hewa a hemahema. Hiki ke alakaʻi i nā maʻi e like me Alzheimer a me Parkinson's. ʻO ka mahanahana, ke kaomi, a me ka loaʻa ʻana o nā molekole ʻē aʻe i loko o ke kelepona he hopena i ka hana pelu.
Ma hope o nā makahiki he nui o ka noiʻi ʻana, ke hoʻāʻo nei ka poʻe ʻepekema e noʻonoʻo pono i ka piʻi ʻana o nā protein.
ʻO ka mea pōmaikaʻi, ke hoʻomaikaʻi nei nā holomua i ka naʻauao artificial i ka hoʻomohala ʻana i ka ʻāpana. Hiki i nā kānaka ʻepekema ke manaʻo pololei i ke ʻano o nā protein ma mua o ka hoʻohana ʻana algorithm mīkini hopu e nānā i ka nui o ka ʻikepili.
Hiki i kēia ke hoʻololi i ka hoʻomohala ʻana i ka lāʻau lapaʻau a hoʻonui i kā mākou ʻike molekala no ka maʻi.
Hiki i nā mīkini ke hana maikaʻi?
Loaʻa nā palena o ka ʻenehana pelu ʻana i ka protein maʻamau
Ke ho'āʻo nei nā kānaka ʻepekema e noʻonoʻo i ka hoʻopili ʻana i ka protein no nā makahiki he mau makahiki, akā ʻo ka paʻakikī o ke kaʻina hana ua lilo kēia i kumuhana paʻakikī.
Hoʻohana ʻia nā ʻano wanana ʻano protein maʻamau i ka hui pū ʻana o nā ʻano hoʻokolohua a me ka hoʻohālike kamepiula, akā naʻe, he mau hemahema kēia mau ʻano.
ʻO nā ʻenehana hoʻokolohua e like me X-ray crystallography a me nuclear magnetic resonance (NMR) hiki ke hoʻopau i ka manawa a me ke kumu kūʻai. A, i kekahi manawa, hilinaʻi nā hiʻohiʻona kamepiula i nā manaʻo maʻalahi, hiki ke alakaʻi i nā wānana kuhihewa.
Hiki iā AI ke lanakila i kēia mau pilikia
Ma kaʻoluʻolu, ʻimi hoʻopunipuni manao ke hāʻawi nei i ka ʻōlelo hoʻohiki hou no ka wānana ʻana i ka ʻōnaehana protein pololei a maikaʻi. Hiki i nā algorithm aʻo mīkini ke nānā i ka nui o ka ʻikepili. A, wehe lākou i nā hiʻohiʻona e poina ai nā kānaka.
ʻO kēia ka hopena i ka hana ʻana i nā lako polokalamu hou a me nā paepae hiki ke wānana i ke ʻano o ka protein me ka pololei ʻole.
ʻO nā Algorithms Aʻo Mīkini Loa Loa no ka Prediction Structure Protein
ʻO ka ʻōnaehana AlphaFold i kūkulu ʻia e Google Deepmind ʻO ka hui kekahi o nā holomua maikaʻi loa ma kēia wahi. Ua loaʻa ka holomua nui i nā makahiki i hala iho nei ma ka hoʻohana ʻana hōʻano haʻawina hohonu e wānana i ke ʻano o nā protein e pili ana i kā lākou mau ʻakika amino.
ʻO nā pūnaewele neural, kākoʻo i nā mīkini vector, a me nā ululāʻau maʻamau kekahi o nā ʻano hana aʻo mīkini e hōʻike ana i ka ʻōlelo hoʻohiki no ka wānana ʻana i ke ʻano o ka protein.
Hiki i kēia mau algorithm ke aʻo mai nā ʻikepili nui. A, hiki iā lākou ke kali i ka pilina ma waena o nā amino acids. No laila, e ʻike kākou pehea e hana ai.
Nā Analyses Co-evolutionary and the First AlphaFold Generation
Ka pomaikai o ʻAlaFold kūkulu ʻia ma luna o kahi ʻōnaehana neural hohonu i kūkulu ʻia me ka hoʻohana ʻana i ka loiloi co-evolutionary. Ua ʻōlelo ka manaʻo o ka co-evolution inā ʻelua mau amino acid i loko o kahi pūmua e hui pū me kekahi, e ulu pū lākou e mālama i kā lākou loulou hana.
Hiki i nā mea noiʻi ke ʻike i nā hui o nā waikawa amino e pili ana i ka hana 3D ma ka hoʻohālikelike ʻana i nā kaʻina amino acid o nā protein like like.
ʻO kēia ʻikepili ke kumu no ka ʻike mua o AlphaFold. Hōʻike ia i ka lōʻihi ma waena o nā hui amino acid a me nā kihi o nā paʻa peptide e hoʻopili iā lākou. Ua ʻoi aku ka maikaʻi o kēia ʻano hana ma mua o ka wānana ʻana i ke ʻano o ka protein mai ke kaʻina, ʻoiai ua kaupalena ʻia ka pololei no nā protein me ka ʻike ʻole ʻia.
AlphaFold 2: He Hana Hana Hou
ʻO AlphaFold2 kahi polokalamu kamepiula i hana ʻia e DeepMind e hoʻohana ana i ka pūnāwai amino acid o ka protein e wānana i ke ʻano 3D o ka protein.
He mea koʻikoʻi kēia no ka mea ʻo ke ʻano o ka protein e kuhikuhi i ke ʻano o ka hana ʻana, a ʻo ka hoʻomaopopo ʻana i kāna hana hiki ke kōkua i ka poʻe ʻepekema e hoʻomohala i nā lāʻau lapaʻau e pili ana i ka protein.
Loaʻa i ka AlphaFold2 neural network ma ke ʻano he hoʻokomo i ke kaʻina amino acid o ka protein a me nā kikoʻī e pili ana i ka hoʻohālikelike ʻana o kēlā kaʻina me nā kaʻina ʻē aʻe i loko o kahi waihona (kapa ʻia kēia he "sequence alignment").
Hana ka neural network i kahi wānana e pili ana i ka hoʻolālā 3D o ka protein e pili ana i kēia hoʻokomo.
He aha ka mea e hoʻokaʻawale iā AlphaFold2?
I ka hoʻohālikelike ʻana i nā ala ʻē aʻe, wānana ʻo AlphaFold2 i ke ʻano 3D maoli o ka protein ma mua o ka hoʻokaʻawale ʻana ma waena o nā ʻakika amino a i ʻole nā kihi ma waena o nā paʻa e hoʻopili ana iā lākou (e like me nā algorithms mua).
I mea e hiki ai i ka neural network ke kali i ka hoʻolālā piha i ka manawa hoʻokahi, ua hoʻopili ʻia ke ʻano i ka hopena a i ka hopena.
ʻO kekahi hiʻohiʻona koʻikoʻi o AlphaFold2 ʻo ia ka hāʻawi ʻana i kahi kuhi o ka hilinaʻi ʻana i kāna wānana. Hōʻike ʻia kēia ma ke ʻano he coding kala ma ke ʻano i manaʻo ʻia, me ka ʻulaʻula e hōʻike ana i ka hilinaʻi kiʻekiʻe a me ka uliuli e hōʻike ana i ka hilinaʻi haʻahaʻa.
He mea pono kēia no ka mea e hōʻike ana i nā ʻepekema e pili ana i ke kūpaʻa o ka wānana.
Ka wānana ʻana i ke kūkulu ʻia ʻana o kekahi mau kaʻina
ʻO ka hoʻonui hou ʻana o Alphafold2, i kapa ʻia ʻo Alphafold Multimer, wānana i ka hui pū ʻana o kekahi mau kaʻina. Loaʻa iā ia nā helu kuhi hewa kiʻekiʻe inā ʻoi aku ka maikaʻi ma mua o nā ʻenehana mua. ʻO %25 wale nō o 4500 mau pūmua protein i wānana maikaʻi ʻia.
ʻO 70% o nā ʻāpana koʻikoʻi o ka hoʻokumu ʻana i ka pilina ua wānana pololei ʻia, akā ʻaʻole pololei ka pili ʻana o nā protein ʻelua. Ke emi iho ka hohonu o ka alignment median ma mua o 30 mau kaʻina, emi nui ka pololei o nā wānana multimer Alphafold.
Pehea e hoʻohana ai i nā wānana Alphafold
Hāʻawi ʻia nā hiʻohiʻona wānana mai AlphaFold i nā ʻano faila like a hiki ke hoʻohana ʻia ma nā ʻano like me nā hale hoʻokolohua. He mea koʻikoʻi e noʻonoʻo i nā kuhi pololei i hāʻawi ʻia me ke kumu hoʻohālike i mea e pale aku ai i nā kuhi hewa.
He mea kōkua nui ia no nā hale paʻakikī e like me nā homomers interwoven a i ʻole nā protein e pelu wale ana i mua o kahi
ligand ʻike ʻole ʻia.
Kekahi mau pilikia
ʻO ka pilikia nui i ka hoʻohana ʻana i nā hale i wānana ʻia ʻo ka hoʻomaopopo ʻana i ka dynamics, ligand selectivity, control, allostery, post-translational changes, and kinetics of binding me ka loaʻa ʻole o ka protein a me ka ʻikepili biophysical.
Machine palapala he a hiki ke hoʻohana ʻia ka noiʻi molecular dynamics e hoʻoponopono i kēia pilikia.
Loaʻa paha kēia mau noiʻi mai ka hoʻolālā kamepiula kūikawā a maikaʻi. ʻOiai ua hoʻokō ʻo AlphaFold i nā holomua nui i ka wānana ʻana i nā ʻōnaehana protein, nui nā mea e aʻo ai ma ke kahua o ka biology structural, a ʻo nā wānana AlphaFold wale nō ke kumu hoʻomaka no ka noiʻi e hiki mai ana.
He aha nā mea hana kupanaha ʻē aʻe?
RoseTTAFold
ʻO RoseTTAFold, i hana ʻia e nā mea noiʻi o ke Kulanui o Wakinekona, e hoʻohana pū ana i nā algorithm aʻo hohonu e wānana i nā ʻōnaehana protein, akā hoʻohui pū ia i kahi ala hou i kapa ʻia ʻo "torsion angle dynamics simulations" e hoʻomaikaʻi i nā kūkulu wānana.
Ua hoʻopuka kēia ʻano hana i nā hopena hoʻoikaika a hiki ke hoʻohana i ka lanakila ʻana i nā palena o nā mea hana hoʻopili protein AI.
trRosetta
ʻO kekahi mea hana ʻē aʻe, ʻo trRosetta, wānana i ka pelu ʻana i ka protein ma o ka hoʻohana ʻana i a kaʻenehana kikowaena aʻo ʻia ma nā miliona o nā kaʻina protein a me nā hale.
Hoʻohana pū ʻo ia i kahi ʻenehana "hoʻohālike i hoʻokumu ʻia" e hana i nā wānana pololei ma ka hoʻohālikelike ʻana i ka protein i hoʻopaʻa ʻia i nā hale i ʻike ʻia.
Ua hōʻike ʻia ua hiki iā trRosetta ke wānana i ke ʻano o nā protein liʻiliʻi a me nā paʻakikī protein.
DeepMetaPSICOV
ʻO DeepMetaPSICOV kahi mea hana ʻē aʻe e kālele ana i ka wānana ʻana i nā palapala ʻāina pili protein. Hoʻohana ʻia kēia mau mea ma ke ʻano he alakaʻi e wānana i ka pelu ʻana i ka protein. Hoʻohana ia haʻawina hohonu nā hoʻokokoke e wānana i ka likelika o ke koena o nā pilina i loko o kahi protein.
Hoʻohana ʻia kēia mau mea e wānana i ka palapala ʻāina pili holoʻokoʻa. Ua hōʻike ʻo DeepMetaPSICOV i ka hiki ke wānana i nā ʻōnaehana protein me ka pololei nui, ʻoiai i ka wā i hāʻule ʻole ai nā ala mua.
He aha ka wā e hiki mai ana?
He mālamalama ka wā e hiki mai ana o AI protein folding. ʻO nā algorithm e pili ana i ka hoʻonaʻauao hohonu, ʻo ia hoʻi ʻo AlphaFold2, ua holomua nui i ka wānana hilinaʻi ʻana i nā kūkulu protein.
Hiki i kēia ʻike ke hoʻololi i ka hoʻomohala ʻana i ka lāʻau lapaʻau ma o ka ʻae ʻana i ka poʻe ʻepekema e hoʻomaopopo maikaʻi i ke ʻano a me ka hana o nā protein, ʻo ia nā pahuhopu therapeutic maʻamau.
Eia nō naʻe, e mau ana nā pilikia e like me ka wānana ʻana i nā complex protein a me ka ʻike ʻana i ke kūlana hana maoli o nā hale i manaʻo ʻia. Pono ka noiʻi hou aʻe e hoʻoponopono i kēia mau pilikia a hoʻonui i ka pololei a me ka hilinaʻi o AI protein folding algorithms.
Eia naʻe, nui nā pōmaikaʻi o kēia ʻenehana, a hiki iā ia ke alakaʻi i ka hana ʻana i nā lāʻau lapaʻau kūpono a pololei.
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