No laila he aha ke ʻano o ka "protein folding"?

ʻO ka maʻi maʻi COVID-19 i kēia manawa ua hoʻokumu i nā pilikia he nui i hauʻoli ka poʻe hackers e hoʻouka. Mai nā pale maka i paʻi ʻia 3D a me nā maka lapaʻau i hana ʻia i ka home a hiki i ka hoʻololi ʻana i kahi ventilator mechanical piha, ʻo ke kahe o nā manaʻo he mea hoʻoulu a hoʻoluʻu puʻuwai. I ka manawa like, aia nā hoʻāʻo e holomua ma kahi ʻē aʻe: i ka noiʻi e pili ana i ka hakakā ʻana i ka maʻi.

ʻIke ʻia, ʻo ka mea nui loa no ka hoʻōki ʻana i ka maʻi maʻi o kēia manawa a ma waho o nā mea a pau e pili ana i kahi ala e hoʻāʻo ai e kiʻi i ke kumu o ka pilikia. Lawe ʻia kēia ʻano "ʻike i kou ʻenemi" e ka papahana ʻo Folding@Home computing. Ua kākau inoa nā miliona o ka poʻe i ka papahana a ke hāʻawi nei i kekahi o ka mana hana o kā lākou mea hana a me nā GPU, no laila e hana ana i ka supercomputer nui loa i ka mōʻaukala.

Akā he aha ke ʻano o kēia mau exaflops? No ke aha e pono ai ke hoʻolei i kēlā mana helu helu i pale ʻana i ka protein? He aha ke ʻano o ka biochemistry e hana nei ma ʻaneʻi, no ke aha e pono ai e pelu nā protein? Eia ka ʻike wikiwiki o ka pelu ʻana i ka protein: he aha ia, pehea ia e hana ai, a no ke aha ia mea nui.

ʻO ka mea mua, ʻo ka mea nui: no ke aha e pono ai nā protein?

ʻO nā protein he mau hale koʻikoʻi. ʻAʻole lākou e hāʻawi wale i nā mea kūkulu hale no nā cell, akā lawelawe pū kekahi ma ke ʻano he enzyme catalysts no kahi kokoke i nā hopena biochemical āpau. ʻO nā squirrels hoʻolālā ai ole ia, enzymatic, he kaulahao loloa amino acids, aia ma kekahi kaʻina. Hoʻoholo ʻia nā hana o nā protein ma kahi o nā amino acids i loaʻa i kekahi mau wahi ma ka protein. Inā, no ka laʻana, pono e hoʻopaʻa ʻia kahi protein i kahi mole i hoʻopiʻi maikaʻi ʻia, pono e hoʻopiha ʻia ka wahi hoʻopaʻa me nā waikawa amino i hoʻopiʻi ʻia.

No ka hoʻomaopopo ʻana i ke ʻano o ka loaʻa ʻana o ka protein i ka hale e hoʻoholo ai i kā lākou hana, pono mākou e hele ma luna o nā kumu o ka biology molecular a me ke kahe o ka ʻike i loko o ke kelepona.

Hoʻohua, a i ʻole hōʻike hoʻomaka nā protein me ka hana nā palapala kākau. I ka wā o ke kākau ʻana, wehe ʻia ka DNA double helix, nona ka ʻike moʻo o ke kelepona, e ʻae ana i nā kumu nitrogen o ka DNA e loaʻa i kahi enzyme i kapa ʻia. RNA polymerase. ʻO ka hana a RNA polymerase ka hana ʻana i kope RNA, a i ʻole transcription, o kahi gene. ʻO kēia kope o kahi gene i kapa ʻia ʻelele RNA (mRNA), he mole hoʻokahi kūpono no ka mālama ʻana i nā ʻoihana protein intracellular, ribosomeska poe e hana ana i ka hana, a i ole hoolaha nā polokina.

Hana nā Ribosomes e like me nā mīkini hui - lawe lākou i ka mRNA template a hoʻohālikelike iā ia me nā ʻāpana liʻiliʻi ʻē aʻe o RNA, hoʻoili RNA (tRNA). Loaʻa i kēlā me kēia tRNA nā ʻāpana hana ʻelua - kahi ʻāpana o ʻekolu kumu i kapa ʻia anticodon, pono e kūlike me nā codons pili o ka mRNA, a me kahi kahua no ka hoʻopaʻa ʻana i kahi waikawa amino kikoʻī no kēia. codon. I ka wā o ka unuhi ʻana, hoʻāʻo wale nā ​​molekole tRNA i loko o ka ribosome e hoʻopaʻa i ka mRNA me ka hoʻohana ʻana i nā anticodons. Inā kūleʻa, hoʻopili ka molela tRNA i kāna ʻakika amino i ka mea mua, e hana ana i ka loulou aʻe ma ke kaulahao o nā waikawa amino i hoʻopili ʻia e ka mRNA.

ʻO kēia kaʻina o nā waikawa amino ka pae mua o ka hierarchy structural protein, ʻo ia ke kumu i kapa ʻia ai. hale hana mua. ʻO ke ʻano holoʻokoʻa ʻekolu-dimensional o kahi protein a me kāna mau hana i loaʻa pololei mai ka hale mua, a hilinaʻi i nā waiwai like ʻole o kēlā me kēia amino acids a me kā lākou pilina me kekahi. Me ka ʻole o kēia mau waiwai kemika a me nā pilina amino acid, polypeptides e noho mau lākou i nā kaʻina laina me ka ʻole o ke ʻano ʻekolu. Hiki ke ʻike ʻia kēia i kēlā me kēia manawa e kuke ai ʻoe i ka meaʻai - ma kēia kaʻina he thermal denaturation ʻekolu ʻāpana o nā protein.

Nā paʻa lōʻihi o nā ʻāpana protein

ʻO ka pae aʻe o ka hale ʻekolu-dimensional, e hele ana ma mua o ka mea mua, ua hāʻawi ʻia i kahi inoa akamai hale lua. Loaʻa iā ia nā paʻa hydrogen ma waena o nā waikawa amino o ka hana pili kokoke. ʻO ke kumu nui o kēia mau pilina paʻa e iho i lalo i ʻelua mau mea: alpha helices и papa inoa beta. Hoʻokumu ka alpha helix i ka ʻāpana wili paʻa o ka polypeptide, aʻo ka pepa beta e hana i ka ʻāpana laulima a ākea. Loaʻa nā ʻano hana ʻelua a me nā waiwai hana, e pili ana i nā hiʻohiʻona o kā lākou mau amino acids. No ka laʻana, inā ʻo ka alpha helix ka nui o nā waikawa amino hydrophilic, like arginine ai ole ia, lysine, a laila e komo paha ia i loko o nā ʻano wai.

ʻO Alpha helices a me nā pepa beta i nā protein. Hoʻokumu ʻia nā paʻa hydrogen i ka wā o ka hōʻike protein.

ʻO kēia mau hale ʻelua a me kā lākou hui pū ʻana i ka pae aʻe o ka ʻōnaehana protein - hale kula kiʻekiʻe. ʻAʻole like me nā ʻāpana maʻalahi o ka hale kiʻekiʻe, ʻo ka hoʻolālā tertiary ka mea nui i ka hydrophobicity. Aia nā kikowaena o ka hapa nui o nā protein i nā waikawa amino hydrophobic, e like me alanine ai ole ia, methionine, a ua kāpae ʻia ka wai mai laila mai ma muli o ke ʻano "greasy" o nā radicals. Hōʻike pinepine ʻia kēia mau hale i nā protein transmembrane i hoʻokomo ʻia i loko o ka membrane bilayer lipid e hoʻopuni ana i nā cell. ʻO nā ʻāpana hydrophobic o nā protein e noho mau i ka thermodynamically paʻa i loko o ka ʻāpana momona o ka membrane, aʻo nā ʻāpana hydrophilic o ka protein e hōʻike ʻia i ka wai wai ma nā ʻaoʻao ʻelua.

Eia kekahi, ua hōʻoia ʻia ka paʻa o nā hale kiʻekiʻe e nā paʻa lōʻihi ma waena o nā waikawa amino. ʻO kahi laʻana maʻamau o ia mau pilina alahaka disulfide, e kū pinepine ana ma waena o ʻelua mau ʻano ʻano cysteine. Inā honi ʻoe i kekahi mea e like me nā hua popopo i loko o kahi salona lauoho i ka wā o kahi kaʻina perm ma ka lauoho o ka mea kūʻai aku, a laila he ʻāpana denaturation kēia o ke ʻano tertiary o ka keratin i loko o ka lauoho, e hana ʻia ma o ka hōʻemi ʻana i nā paʻa disulfide me ka kokua o ka sulfur thiol huikau.

Hoʻokūpaʻa ʻia ka hoʻolālā Tertiary e nā pilina lōʻihi e like me ka hydrophobicity a i ʻole nā ​​mea paʻa disulfide

Hiki ke loaʻa nā paʻa disulfide ma waena ʻo ka cysteine nā radical i loko o ke kaulahao polypeptide hoʻokahi, a i ʻole ma waena o nā cysteine ​​mai nā kaulahao piha like ʻole. Hana ʻia nā pilina ma waena o nā kaulahao like ʻole quaternary pae o ka hana protein. ʻO kahi laʻana maikaʻi loa o ka hoʻolālā quaternary hemoglobin i loko o kou koko. ʻO kēlā me kēia mole hemoglobin he ʻehā mau globins like, nā ʻāpana protein, paʻa kēlā me kēia mea i kahi kūlana kūikawā i loko o ka polypeptide e nā alahaka disulfide, a pili pū kekahi me kahi mole heme i loko o ka hao. Hoʻopili ʻia nā globins ʻehā a pau e nā alahaka disulfide intermolecular, a hoʻopaʻa ʻia ka mole holoʻokoʻa i kekahi mau molekole ea i ka manawa hoʻokahi, a hiki i ʻehā, a hiki ke hoʻokuʻu iā lākou e like me ka mea e pono ai.

Hoʻohālike i nā hale no ka ʻimi ʻana i ka lāʻau no ka maʻi

Hoʻomaka nā kaulahao polypeptide e pelu i ko lākou ʻano hope i ka wā o ka unuhi ʻana, ʻoiai e puka ana ke kaulahao ulu i waho o ka ribosome, e like me kahi ʻāpana o ka uea hoʻomanaʻo-alloy hiki ke lawe i nā ʻano paʻakikī ke hoʻomehana ʻia. Eia naʻe, e like me nā mea maʻamau i ka biology, ʻaʻole maʻalahi nā mea.

I loko o nā pūnaewele he nui, hoʻololi nui nā genes i unuhi ʻia ma mua o ka unuhi ʻana, me ka hoʻololi nui ʻana i ke ʻano kumu o ka protein i hoʻohālikelike ʻia me ke kaʻina kumu maʻemaʻe o ka gene. I kēia hihia, ʻimi pinepine nā mīkini unuhi i ke kōkua o nā chaperones molecular, nā protein e hoʻopaʻa manawaleʻa i ke kaulahao polypeptide nascent a pale iā ia mai ka lawe ʻana i kekahi ʻano waena, a laila ʻaʻole hiki iā lākou ke neʻe i ka hope.

ʻO kēia ka mea e ʻōlelo ai ʻo ka wānana ʻana i ke ʻano hope o kahi protein ʻaʻole ia he hana koʻikoʻi. No nā makahiki he mau makahiki, ʻo ke ala wale nō e aʻo ai i ke ʻano o nā protein ma o nā ʻano kino e like me X-ray crystallography. ʻAʻole hiki i ka hopena o nā makahiki 1960 ka hoʻomaka ʻana o nā mea hoʻokalakupua biophysical e kūkulu i nā kumu hoʻohālikelike o ka hoʻopili ʻana i ka protein, me ka nānā nui ʻana i ke ʻano hoʻohālike o ka hale kiʻekiʻe. Pono kēia mau ʻano a me kā lākou poʻe mamo i ka nui o ka ʻikepili hoʻokomo i ka hoʻohui ʻana i ka hana mua - no ka laʻana, nā papa o nā kihi hoʻopaʻa amino acid, nā papa inoa o ka hydrophobicity, nā mokuʻāina i hoʻopaʻa ʻia, a me ka mālama ʻana i ka hale a me ka hana ma luna o nā manawa evolutionary - nā mea a pau i mea e hiki ai. e koho i ka mea e like me ka protein hope loa.

ʻO nā ʻano helu helu o kēia lā no ka wānana ʻana i ka hana lua, e like me nā mea e holo ana ma ka pūnaewele Folding@Home, hana me ka pololei o 80% - maikaʻi loa ia e noʻonoʻo i ka paʻakikī o ka pilikia. ʻO ka ʻikepili i hana ʻia e nā hiʻohiʻona wānana i nā protein e like me ka SARS-CoV-2 spike protein e hoʻohālikelike ʻia me ka ʻikepili mai nā haʻawina kino o ka maʻi. ʻO ka hopena, hiki ke loaʻa i ke ʻano kikoʻī o ka protein a, malia paha, e hoʻomaopopo i ke ʻano o ka hoʻopili ʻana o ka maʻi i nā mea loaʻa. ʻO ka enzyme hoʻololi i ka angiotensin 2 he kanaka i loko o ka ʻōpū hanu e alakaʻi ana i ke kino. Inā hiki iā mākou ke noʻonoʻo i kēia ʻano hana, hiki iā mākou ke loaʻa nā lāʻau lapaʻau e pale ai i ka hoʻopaʻa ʻana a pale i ka maʻi.

ʻO ka noiʻi hoʻopili protein ma ka puʻuwai o ko mākou hoʻomaopopo ʻana i nā maʻi a me nā maʻi he nui ʻoiai ke hoʻohana nei mākou i ka pūnaewele Folding@Home e noʻonoʻo ai pehea e lanakila ai iā COVID-19, a mākou i ʻike ai e pahū ana i ka ulu ʻana i kēia mau lā, lanakila ka pūnaewele. e noho palaualelo no ka hana loihi. He mea hana noiʻi kūpono ia no ke aʻo ʻana i nā ʻano protein e hoʻopaʻa nei i nā ʻumi o nā maʻi misfolding protein, e like me ka maʻi Alzheimer a i ʻole ka maʻi ʻokoʻa ʻo Creutzfeldt-Jakob, i kapa pinepine ʻia he maʻi pipi pupule. A ke ʻike ʻole ʻia kahi maʻi ʻē aʻe, e mākaukau mākou e hoʻomaka e hakakā hou.

Source: www.habr.com