
protein ghadana pravachanam

oru proteente amino assid shreniyil ninnulla trimana gadanayude anumaanamaan protein ghadana pravachanam-athaayath praadhamika ghadanayil ninnu athinte dvitheeya, thritheeya gadanayude pravachanam. ghadana pravachanam protein roopakalppanayude vipareeta prashnatthil ninnu vyathyasthamaan. computational biology pinthudarunna ettavum pradhanappetta lakshyangalilonnaan protein ghadana pravachanam; vaidyashaasthrathilum (udaaharanathinu, marunnu roopakalppanayil) biotechnology (udaaharanathinu, puthiya ensaimukalude roopakalppanayil) ithu pradhaanamaan.
1994 muthal, nilavile reethikalude prakadanam casp pareekshanatthil (protein ghadana pravachanathinulla saankethikavidyakalude nirnaayaka vilayiruthal) vaarshikamaayi vilayiruthunnu. community project kemiyo3dii protein ghadana pravachana web servarukalude thudarchayaaya vilayiruthal nadathunnu.
protein ghadanayum padawali.
pepttaid bondukalaal bandhippikkappedunna amino aasidukalude shringalakalaanu proteinukal. cα aattathile φ, si ennee rund tortion konukalil pradhana shringalayude bhramanam kaaranam eee shringalayude niravadhi roopeekaranangal saadhyamaan (chithram kaanuka). proteinukalude trimana gadanayile vyathyaasangalkk eee roopeekarana vazhakkam kaaranamaakunnu. shringalayile pepttaid bondukal dhruvamaan, i.iii. hydrajan boond sweekarthaavaayum hydrajan boond daathaavaayum pravartthikkaan kazhiyunna enh groupilum pravartthikkaan kazhiyunna carbonyl groupil positteev, negatteevu chaarjukal (bhagika chaarjukal) avaa verthirikkunnu. athinaal eee grouppukalkku protein ghadanayil edapedaanaakum. proteinukalil kooduthalum 20 vyathyastha tharam ell-α-amino aasidukal (proteinogenic amino aasidukal) adangiyirikkunnu. side cheyinte rasathanthramanusarichu ivaye tharamthirikkaam, ithu oru pradhana gadanaaparamaaya punk vahikkunnu. ettavum cheria side cheyin ullathinaal glycine oru prathyeka sthaanam ettedukkunnu, oru hydrajan aattam maathrame ulloo, athinaal protein gadanayile praadeshika vazhakkam vardhippikkaan kazhiyum. maruvashathu sisttainin mattoru sisttain avashishtavumaayi prathipravartthichu oru sisttain roopappeduthaanum athuvazhi muzhuvan ghadanayeyum sthirappeduthunna oru cross link roopeekarikkaanum kazhiyum.
protein ghadanaye α helixukal, β sheettukal thudangiya dvitheeya ghadana gadakangalude oru sreniyaayi kanakkakkaam. eee dvitheeya gadanakalil, praadeshikamaayi ayalthulla amino aasidukalude pradhana shringalayaaya enh, qoo grouppukalkkidayil echu-bondukalude pathiv paattenukal roopappedunnu, koodaathe amino aasidukalkk samanamaaya φ, si ennivayundu.
konukal.
eee dvitheeya gadanakalude roopeekaranam pepttaid bondukalude hydrajan bonting seshiye kaaryakshamamaayi thripthippeduthunnu. hydrophobic parithasthithiyil dvitheeya gadanakal protein koril karsanamaayi paaykk cheyyaan kazhiyum, pakshe avaykku dhruva protein uparithalathilum avatharippikkan kazhiyum. oro amino assid side cheyinum parimithamaaya alavum aduthulla mattu side cheyinukalumaayi parimithamaaya ennam saadhyamaaya edapedalukalum undu, ithu molecular modelingilum alainmentukalilum kanakkiledukkenda oru saahacharyamaan.
α-helix.
proteinukalile ettavum samriddhamaaya dvitheeya gadanayaanu α-helix. oro naalaamathe avashishtathinum idayil roopappedunna oru echu-bondullah oro tenilum α-helixil 3.6 amino aasidukal undu; sharashari neelam 10 amino aasidukal (3 tenukal) allengil 10 Â aanenkilum 5 muthal 40 vare (1.5 muthal 11 tenukal) vyathyaasappedunnu. echu-bondukalude vinyaasam helixinte amino attathu bhagika positteev charjullah helixinu oru dvidhruva nimisham srishtikkunnu. eee pradeshathinu swatantra enh grooppukalullathinaal, ithu phosphettukal polulla negatteevu charjju cheytha grouppukalumaayi samvadikkum. α-helikkukalude ettavum saadhaaranamaaya sthaanam protein korukalude uparithalathilaan, avide avaa jaleeya paristhithiyumaayi oru interface nalkunnu. helixinte akathe vashath hydrophobic amino aasidukalum puram vashath hydrophilic amino aasidukalum undu. athinaal, shringalayiludaneelamulla naalu amino aasidukalil oro moonnil oru bhaagavum hydrophobic aayirikkum, ithu valare eluppathil kandethaan kazhiyunna oru paatten aanu. lucine sipper roopathil, aduthulla rund helikkukalude abhimukhabhaagangalil lyoosinsinte aavarthichulla paatten roopathekkurichu valare pravachikkunnu. eee aavarthichulla paatten kaanikkan oru helical wheel plott upayogikkaam. protein corillo sellular membranukalilo kuzhichittirikkunna mattu α-helikkukalkk hydrophobic amino aasidukalude uyarnnathum kooduthal pathivayathumaaya vitharanamundu, avaa atharam gadanakalekkurichu valareyadhikam pravachikkunnu. uparithalathil thurannukaattappedunna helikkukalil hydrophobic amino aasidukalude anupatham kuravaanu. amino aasidinte alavu oru α-heelikkal mekhalaye pravachikkaan kazhiyum. alanine (eiii), glutamic assid (iii), lucine (ell), methionin (emm) ennivayaal sambannamaaya pradeshangalum prolin (pii), glycine (jii), tyrosine (vaii), serin (kall) ennivayil daridramaaya pradeshangalum oru α-helix roopappeduthunnu. prolin oru α-helixine asthirappeduthukayo thakarkkukayo cheiyunnu, pakshe neelamulla helixukalil ithu undakam, ithu oru valavu undaakkunnu.
β-sheett.
shringalayude oru bhaagathe sharashari 5-10 thudarchayaaya amino aasidukalkkum shringalayude thaazheyulla mattoru 5-10 num edayilulla echu-bondukalaanu β-sheettukal roopappeduthunnathu. parasparabandhithamaya pradeshangal aduthaayirikkaam, athinidayil oru hraswa lupe allengil valare akale, mattu gadanakalkkidayil. oro shringalayum ore dishayilekku oodukayum oru samanthara sheett roopappedukayum cheyyaam, matellaa shringalakalum vipareeta raasa dishayil pravartthikkukayum oru samanthara virudha sheett roopappedukayum cheyyaam, allengil changalakal samaantharavum samaantharavumaayirikkaam. samaantharavum virudhavumaaya samanthara krameekaranangalil echu bondinginte paatten vyathyasthamaan. sheettinte aantharika izhakalile oro amino assid ayal amino aasidukalumaayi rund echu-bondukal roopappeduthunnu, athesamayam puram izhakalile oro amino assid oru aantharika izhayumaayi oru boond maathrame roopappeduthoo. sheettinu kuruke ezhakalilekku lamba konukalil nokkumbol, kooduthal vidooramaaya izhakal idamkaiyyan twist roopappeduthunnathinaayi alpam ethir gadikaaradishayil thirikkunnu. sii. eiii.-attangal sheettinu mukalilum thaazheyum oru plettad ghadanayil marimari varunnu, amino aasidukalude aarr side grouppukal plettukalkk mukalilum thaazheyum marimari varunnu. sheettukalile amino aasidukalude φ, si konukal ramachandran plottinte oru pradeshathu ganyamaayi vyathyaasappedunnu. α-helikkukalude sthaanathekkaal β-sheettukalude sthaanam pravachikkaan kooduthal budhimuttaanu. onniladhikam sequence alainmentukalile amino assid vyathiyaanam kanakkiledukkumbol sahacharyam oru paridhivare mechappedunnu.
looppukal.
proteente chila bhaagangalkk trimana gadanayundu, pakshe avaa sthiramaaya gadanakalonnum roopappeduthunnilla. avaye proteinukalude kramarahithamo anaavrithamo aaya bhaagangalumaayo allengil sthiramaaya trimana gadanayillaatha anaavritha polypeptide shringalayaaya kramarahithamaya koyilumaayo thettidharikkaruthu. β-sheettukalum α-helixukalum bandhippikkunnathinaal eee bhaagangale palappozhum looppukal ennu vilikkunnu. looppukal saadhaaranayaayi protein uparithalathilaan sthithicheyyunnathu, athinaal avayude avashishtangalude mutationukal kooduthal eluppathil sahikkappedunnu. oru sequence alainmentinte oru prathyeka pradeshathu kooduthal pakarakkar, ulppeduthalukal, illaathaakkalukal enniva orupakshe oru looppinte soochanayaayirikkaam. genomic dnayile intronukalude sthaanangal encode cheytha proteinile looppukalude sthaanangalumaayi bandhappettirikkam. looppukalkk charjju cheythathum dhruva amino aasidukalum undu, avaa palappozhum sajeevamaaya saittukalude oru gadakamaanu.
protein vargeekaranam.
gadanaaparavum kramaparavumaaya saamyam anusarichu proteinukale tharamthirikkaam. gadanaaparamaaya vargeekaranathinaayi, melpparanja khandikayil vivarichirikkunna dvitheeya gadanakalude valuppangalum speshyal krameekaranangalum ariyappedunna trimana gadanakalumaayi thaarathamyam cheiyunnu. sequence samaanathaye adisthaanamaakkiyulla vargeekaranamaanu charitraparamaayi aadyamaayi upayogichathu. thudakkathil, muzhuvan sequenceukaludeyum vinyaasangale adisthaanamaakkiyulla saamyam avatharippichu. pinneedu, samrakshitha amino assid paattenukalude sambhavathinte adisthaanathil proteinukale tharamthirichu. eee skeemukalil onno athiladhikamo proteinukale tharamthirikkunna daattabesukal labhyamaan.
protein vargeekarana padhathikal pariganikkumbol, niravadhi nireekshanangal manassil sookshikkendathu pradhaanamaan. onnamathaayi, vyathyastha parinaama uthbhavangalil ninnulla rund thikachum vyathyasthamaaya protein sequenceukal samanamaaya gadanayilekku madakkiyekkaam. neremarichu, oru prathyeka gadanaykkulla oru purathana jeeninte kramam ore samayam ore adisthaana gadanaaparamaaya savisheshathakal nilanirthikkondu vyathyastha speesheesukalil ganyamaayi vyathichalichirikkam. atharam sandarbhangalil avasheshikkunna eathenkilum sequence saamyam thirichariyunnathu valare budhimuttulla oru joliyayirikkaam. randaamathaayi, parasparam allengil moonnaamathe sreniyumaayi ganyamaaya alavil sequence saamyam pankidunna rund proteinukalum parinaama uthbhavam pankidunnu, koodaathe chila gadanaaparamaaya savisheshathakalum pankidanam. ennirunnaalum, parinaamasamayathu jeane thanippakarppum janithaka punakrameekaranangalum puthiya jeane pakarppukalkk kaaranamakum, avaykku puthiya pravartthanavum ghadanayum ulla proteinukalaayi parinamikkaan kazhiyum.
protein gadanakalum shrenikalum tharamthirikkaan upayogikkunna padangal.
proteinukal thammilulla parinamaparavum gadanaaparavumaaya bandhangalkkayi saadhaaranayaayi upayogikkunna padangal chuvade pattikappedutthiyirikku. proteinukalil kaanapedunna vividha tharatthilulla gadanaaparamaaya savisheshathakalkk niravadhi adhika padangal upayogikkunnu. atharam padangalude vivaranagal kaath websait, proteinukalude gadanaaparamaaya vargeekaranam (scope) websait, swis bioinformatics exacy websaittile oru glaxo velkkam tutorial ennivayil kaanam.
dvitheeya ghadana.
amino assid sreniyekkurichulla arivine maathram adisthaanamaakki proteinukalude praadeshika dvitheeya gadanakal pravachikkaan lakshyamidunna bioinformaticsile oru koottam saankethikavidyakalaanu dvitheeya ghadana pravachanam. proteinukale sambandhichidatholam, amino assid shreniyude pradeshangale alfa helixukal, beetaa straandukal (palappozhum "extended" conformations ennu ariyappedunnu) allengil tenukal enningane nirnnayikkunnath oru pravachanatthil ulppedunnu. oru pravachanatthinte vijayam nirnnayikkunnath athine dii. ezz. ezz. pii. algorithathinte (allengil samanamaaya iii.) falangalumaayi thaarathamyam cheythaanu.jii. stride) proteente kristtal ghadanayil prayogikkunnu. proteinukalile transmembran helikkukalum coiled koyilukalum polulla nannayi nirvachikkapetta prathyeka paattenukal kandethunnathinayi prathyeka algorithangal vikasippichittund.
proteinukalile dvitheeya ghadana pravachanatthinte ettavum mikacha aadhunika reethikal mesheen laning sequence alainmentukalum upayogichathinu sesham 80 sathamaanam krithyatha kaivarikkumennu avakashappettu; eee uyarnna krithyatha fold recognition abb initio protein structure pravachanavum mechappeduthunnu, gadanaaparamaaya roopangalude vargeekaranam, sequence alainmentukalude parishkkaranam enniva mechappeduthunnu. nilavile protein dvitheeya ghadana pravachana reethikalude krithyatha live bench, ivaa thudangiya prathivaara maanadandangalil vilayiruthunnu.
pashchaathalam.
1960kalilum 1970 kalude thudakkathilum avatharippicha dvitheeya ghadana pravachanatthinte aadyakaala reethikal, alfa helikkukal thirichariyaan saadhyathayullathil shradha kendreekarikkukayum pradhaanamaayum helix-koyil transition modalukale adisthaanamaakkiyullavayumanu. beetaa sheettukal ulppedunna kooduthal krithyamaaya pravachanangal 1970-kalil avatharippikkukayum ariyappedunna pariharikkapetta gadanakalil ninnu uruthirinja probability paaraameettarukale adisthaanamaakkiyulla sthithivivarakkanakku vilayiruthalukale aasrayikkukayum cheythu. orotta shreniyil prayogikkunna eee reethikal saadhaaranayaayi ekadesham 60-65% krithyathayullathum palappozhum beetta sheettukal pravachikkappedaathathumaanu. 1980kall muthal, protein gadanakalude pravachanathinu krithrima neural netvarkkukal prayogikkappettittundu.
amino aasidukalude oru allined nirayude nettu secondary structure propensity kanakkakkikkondu onniladhikam sequence alainmentil niravadhi homologous sequenceukal oresamayam vilayiruthunnathiloode dvitheeya gadanakalude parinaama samrakshanam prayojanappedutthaam. ariyappedunna protein gadanakalude valia daattaabesukalumaayum neural nettukal, support vekttar mesheenukal thudangiya aadhunika mesheen laining reethikalumaayum samyojippichu, eee reethikalkku globular proteinukalil mothatthilulla 80 sathamaanam vare krithyatha nedaan kazhiyum. dvitheeya gadanakalude attathinaduthulla dii. ezz. ezz. pii assainmentile prathyekathakal kaaranam, praadeshika roopeekaranangal thaddesheeya saahacharyangalil vyathyaasappedunnunde packing parimithikal kaaranam paralukalil orotta roopeekaranam anumanikkaan nirbandhitharaayekkaavunna, krithyathayude saidhaanthika uyarnna paridhi ekadesham 90 sathamaanamaanu. koodaathe, saadhaarana dvitheeya ghadana pravachana reethikal dvitheeya gadanayude roopeekaranathil thritheeya gadanayude swaadheenathinu kaaranamakunnilla; udaaharanathinu, helix aakaan saadhyathayulla oru sreniye proteininte beetaa-sheett mekhalaykkullil sthithicheyyukayum athinte side cheyinukal avarude ayalkkaarumaayi nannayi paaykk cheyyukayum cheythaal beetaa-staand conformation sweekarikkaan kazhinjekkum. proteininte pravartthanavumaayo paristhithiyumaayo bandhapetta naadakeeyamaaya roopeekarana maattangalkk praadeshika dvitheeya ghadanaye mattaanum kazhiyum.
charitraparamaaya kaazhchappaad.
innuvare, 20-ladhikam vyathyastha dvitheeya ghadana pravachana reethikal vikasippichittund. oro tharatthilulla dvitheeya ghadanayilum oro amino aasidinteyum roopathinte aapekshika aavruthikalil ninnu nirnnayikkappedunna probability paaraameettarukale pradhaanamaayum aasrayikkunna chau-fassman reethiyaanu aadyathe algorithangalilonnu. 1970 kalude madhyathil pariharicha gadanakalude cheria saambilil ninnu nirnnayikkappedunna yadhaartha chau-fassman paaraamettarukal, aadhunika reethikalumaayi thaarathamyappeduthumbol mosham phalangal nalkunnu, ennirunnaalum paaraameettaraiseshan aadyamaayi prasidheekarichathumuthal update cheythittundu. dvitheeya gadanakal pravachikkunnathil chau-fassman reethi ekadesham 50-60% krithyamaanu.
adutha sradheyamaaya prograam gorr reethi oru vivara sidhaanthathe adisthaanamaakkiyulla reethiyaanu. ithu bayeshyan anumaanathinte kooduthal sakthamaaya probabilistik saankethikavidya upayogikkunnu. oro amino asidinum oru prathyeka dvitheeya ghadana undakanulla saadhyatha mathramalla, ayalkkaarude sambhavanakal kanakkileduthu oro ghadanayum anumaanikkunna amino aasidinte vyavasthaapitha saadhyathayum gorr reethi kanakkiledukkunnu (ayalkkaarkk athe gadanayundennu ithu anumanikkunnilla). prolin, glycine thudangiya cheria ennam amino aasidukalkk maathrame amino assid gadanaaparamaaya pravanathakal shakthamaayulloo ennathinaal eee sameepanam chau, fassman ennivayekkaal kooduthal sensiteevum krithyavumaanu. pala ayalkkaaril ninnum oororutharudeyum durbalamaaya sambhavanakal mothatthil sakthamaaya phalangal nalkum. yadhaartha gorr reethi ekadesham 65 sathamaanam krithyathayullathum beetta sheettukalekkaal alfa helisukal pravachikkunnathil naadakeeyamaayi kooduthal vijayakaravumaan, avaa palappozhum looppukalo asamghaditha pradeshangalo aayi thettidharikkappedunnu.
mattoru valia chuvaduveppu, mesheen laining reethikal upayogikkuka ennathaayirunnu. aadyathe krithrima neural network reethikal upayogichu. oru pariseelana settaayi avar dvitheeya gadanakalude prathyeka krameekaranangalumayi bandhapetta pothuvaaya sequence motifukal thirichariyaan pariharikkapetta gadanakal upayogikkunnu. eee reethikal avayude pravachanagalil 70 sathamaanathiladhikam krithyathayullavayaanenkilum, hydrajan bonting paattenukalude vilayiruthal anuvadikkunna trimana gadanaaparamaaya vivarangalude abhavam kaaranam beetta straandukal ippozhum kurachukoodi pravachikkappedunnu, ithu oru samboornna beetta sheettinte saannidhyathin aavashyamaaya vipuleekritha roopeekaranathinte roopeekaranathe prolsaahippikkum. protein dvitheeya ghadana pravachanathinaayi neural nettvarkkukale adisthaanamaakkiyulla ettavum ariyappedunna prograamukalaan sipred, jeey. pii. aarr. dii. enniva. aduthathaayi, stattistikkal reethikal upayogichu thirichariyaan prayaasamulla thirivukalude sthaanangal pravachikkaan support vekttar mesheenukal prathyekichum upayogapradamaanennu theliyikkappettittund.
mesheen laining teknikkukalude vipuleekaranangal proteinukalude kooduthal sookshumamaaya praadeshika gunangal pravachikkaan shramikkunnu, athaayath niyukthamallaatha pradeshangalile nattellu dihedral konukal. eee prashnathinu ezz. vii. emm.-kalum neural nettvarkkukalum prayogichittundu. aduthide, yadhaartha moolyamulla tortion konukal nattellu-x upayogichu krithyamaayi pravachikkanum abb initio ghadana pravachanathinaayi vijayakaramaayi upayogikkaanum kazhiyum.
mattu mechappeduthalukal.
protein shrenikku purame, dvitheeya gadanayude roopeekaranam mattu gadakangale aashrayichirikkunnuvennu report cheyyappedunnu. udaaharanathinu, dvitheeya ghadana pravanathakal praadeshika paristhithi, avashishtangalude layaka labhyatha, protein gadanaaparamaaya klaas, proteinukal labhikkuna jeevikal ennivayeppolum aashrayichirikkunnuvennu report cheyyappedunnu. atharam nireekshanangalude adisthaanathil, protein structural klaas, sheshipp axus cheyyaavunna uparithala vistheernnam, kondaakt nambar vivarangal ennivayekkurichulla vivarangal cherkkunnathiloode dvitheeya ghadana pravachanam mechappeduthaan kazhiyumennu chila padanangal theliyichittundu.
moonnaam ghadana.
protein ghadana pravachanatthinte praayogika punk ippol ennathekkaalum pradhaanamaan. manushya genome project polulla aadhunika valia thothilulla dna sequencing sramangaliloodeyaanu valia alavil protein sequence daatta nirmmikkunnath. gadanaaparamaaya genomicsile samooha vyaapakamaayi sramangal nadannittum, pareekshanaathmakamaayi nirnnayikkappetta protein gadanakalude outtputtu-saadhaaranayaayi samayamedukkunnathum thaarathamyena chelaveriyathumaaya ex-reey christalography allengil enmr spectroscopy-protein seekwansukalude aouttputtil valare pinnilaanu.
protein ghadana pravachanam valare budhimuttullathum pariharikkappedaathathumaaya oru samrambhamaayi thudarunnu. protein rahita oorjjathinte kanakkukoottalum eee oorjjathinte aagola minimum kandethalumanu rund pradhana prasnangal. oru protein ghadana pravachana reethi jyothishaasthraparamaayi valuthaya protein gadanakalude idam paryavekshanam cheyyanam. eee prasnangal "thaarathamya" allengil homology modelingilum madakka thirichariyal reethikalilum bhaagikamaayi marikadakkaan kazhiyum, athil samshayaaspadamaaya protein mattoru homologous proteente pareekshanaathmakamaayi nirnnayikkappetta gadanayodu aduthulla oru ghadana sweekarikkunnu enna anumaanathaal thirayal idam vettimattunnu. maruvashathu, dii novo protein ghadana pravachana reethikal eee prasnangal vyakthamaayi pariharikkanam. protein ghadana pravachanatthile purogathiyum velluvilikalum shang avalokanam cheythittundu.
modeling cheiyunnathinu munbu.
rosetta polulla mikka thritheeya ghadana modeling reethikalum single protein domainukalude thritheeya ghadana modeling cheiyunnathinu opttimais cheythathaanu. domaine paazhsing allengil domaine boundari pravachanam ennu vilikkunna oru ghattam saadhaaranayaayi oru proteine saadhyathayulla gadanaaparamaaya domainukalaayi vibhajikkaan aadyam cheiyunnu. bakkiyulla moonnaam ghatta ghadana pravachanatthilennapole, ithu ariyappedunna gadanakalil ninno allengil "abb initio" yill ninno thaarathamyappeduthumbol (saadhaaranayaayi mesheen laining, koveriyeshan sahaayathode) maathrame cheyyaan kazhiyoo. vyakthigatha domainukalude gadanakal domaine assembly enna prakriyayil orumichu doock cheyth anthima thritheeya ghadana roopappeduthunnu.
"abb initio" protein modeling.
oorjjavum shakalangalum adisthaanamaakkiyulla reethikal.
"abb initio"-allengil "dii novo"-protein modeling reethikal trimana protein modalukal nirmmikkaan shramikkunnu "aadyam muthal", athaayath.iii.munbu pariharicha gadanakale (nerittu) adisthaanamaakkiyullathalla bhauthika thathwangale adisthaanamaakkiyullathaanu. protein madakkal anukarikkaan shramikkukayo allengil saadhyamaaya pariharangal tirayan chila yaadruchika reethi prayogikkukayo cheiyunna niravadhi nadapadikramangalundu (athaayath.iii.anuyojyamaaya oorjja pravartthanatthinte aagola opttimaiseshan). eee nadapadikramangalkku vishalamaaya computational vibhavangal aavasyamaanu, athinaal cheria proteinukalkku maathrame ithu nadappaakkiyittulloo. valia proteinukalkkulla protein ghadana "dii novo" pravachikkaan mikacha algorithangalum sakthamaaya suuppar computerukal (blue jeane allengil emm. dii. grap-3 polullava) allengil distributed computing (<aii. dii. 2>, human proteom folding project, <aii. dii. 1> enniva polullava) polulla valia computational vibhavangalum aavasyamaanu. eee computational thadassangal vishaalamaanenkilum, gadanaaparamaaya genomicsinte (pravachichatho pareekshanaathmakamo aaya reethikal) saadhyathayulla nettangal "abb initio" ghadana pravachanatthe oru sajeeva gaveshana mekhalayaakkunnu.
2009 leeii kanakkanusarichu, oru 50 avashishta protein oru suuppar computeril 1 millisecondinaayi aattam-bye-aattam simulettu cheyyaan kazhiyum. 2012 leeii kanakkanusarichu, oru puthiya graphics card kooduthal sankeernamaaya algorithangalum upayogichu oru staanderd desktoppil thaarathamyappeduthaavunna sthira-avastha sample cheyyaan kazhiyum. parukkan modeling upayogichu valare valia simuleshan timescaleukal nedaan kazhiyum.
3dii kondaakttukal pravachikkunnathinulla parinaama kovereshan.
1990kalil sequencing kooduthal saadhaaranamaayitheernnathode niravadhi grouppukal parasparabandhithamaya mutationukal pravachikkaan protein sequence alainmentukal upayogichu, eee sahavikasita avashishtangal moonnaam ghadana pravachikkaan upayogikkaamenn pratheekshichirunnu (enmr polulla pareekshanathmaka nadapadikramangalil ninnulla dooraparidhikalumaayulla saamyam upayogichu). eaka avashishta mutationukal alppam doshakaramaakumbol, avashishta-avashishta edapedalukal punasthaapikkunnathinu kompansettari mutationukal sambhavikkam ennathaanu anumaanam.
eee aadyakaala pravartthanam protein sequenceukalil ninnulla parasparabandhitha mutationukal kanakkakkaan "local" reethikal ennariyappedunnava upayogichu, ennaal oro jody avashishtangaleyum matellaa jodikalil ninnum swathanthramaayi kanakkaakkunnathinte falamaayundaakunna paroksha thettaaya parasparabandhangal anubhavichu.
2011-ll, vyathyasthavum ithavanathe "aagola" sthithivivarakkanakku sameepanavum, pravachicha sahavikasita avashishtangal oru proteente 3 dii madangu pravachikkaan paryaapthamaanennu theliyichu, mathiyaya sequenceukal labhyamaan (> 1,000 homologous sequenceukal aavasyamaanu). eee reethi, evefold, homology modeling, threading allengil 3 dii structure sakalangal enniva upayogikkunnilla, koodaathe noorukanakkinu avashishtangalulla proteinukalkku polum oru staanderd pezhsanal computeril pravarthippikkaan kazhiyum. pareekshanaathmakamaayi pariharikkappedaatha transmembran proteinukalude pravachanam ulppede, ithu upayogichum anubandha sameepanagal upayogichum pravachicha kondaakttukalude krithyatha ippol ariyappedunna niravadhi gadanakalilum kondaakt maappukalilum pradarshippichittundu.
thaarathamya protein modeling.
thaarathamya protein modeling munbu pariharicha gadanakale prarambha poyintukalaayo templettukalaayo upayogikkunnu. yadhaartha proteinukalude ennam valare valuthaanenkilum, mikka proteinukalum ulppedunna parimithamaaya oru koottam thritheeya gadanaaparamaaya roopangal undennu thonnunnathinaal ithu falapradamaanu. dasalakshakkanakkinu vyathyastha proteinukal undengilum prakrithiyil ekadesham 2,000 vyathyastha protein madakkukal maathrame ulloo ennu abhipraayappedunnu. thaarathamya protein modelinginu ghadana pravachanatthile parinaama koveriyeshanumaayi samyojippikkaan kazhiyum.
eee reethikale rund grouppukalaayi tirikkaam
side-cheyin roopeekaranangalude modeling.
amino assid side cheyinukalude krithyamaaya packing protein ghadana pravachanatthil oru prathyeka prashnathe prathinidheekarikkunnu. side-cheyin jyamiti pravachikkunna prashnam prathyekamaayi abhisambodhana cheiyunna reethikalil dedd-end elemination svayam sthirathayulla sharashari feeld reethikalum ulppedunnu. kuranja oorjjamulla side cheyin roopeekaranangal saadhaaranayaayi karkkashamaaya polypeptide nattellilum rotamarukal ennariyappedunna oru koottam vyathiriktha side cheyin roopeekaranangalum upayogichaanu nirnnayikkunnath."modalinte mothatthilulla oorjjam kuraykkunna rotamarukalude koottam thirichariyaan reethikal shramikkunnu.
eee reethikal rotamer librarikal upayogikkunnu, avaa proteinukalile oro avashishta tharatthinum anukoolamaaya krameekaranangalude shekharamaanu. rotamer librarikalil roopeekaranam, athinte aavruthi, sharashari dihedral konukalekkurichulla staanderd vyathiyanangal ennivayekkurichulla vivarangal adangiyirikkaam, avaa saambilingil upayogikkaam. staggered (60°, 180°,-60°) moolyangalkku sameepam tetrahedral kaarbanukalude nireekshicha krameekaranangal klasttar cheiyunnathu polulla proteinukalude ariyappedunna pareekshanathmaka gadanakalile side-cheyin krameekaranangalude gadanaaparamaaya bioinformatics allengil mattu sthithivivarakkanakku vishakalanagalil ninnaan rotamer librarikal uruthirinjathu.
rotamer librarikal nattellu-swathanthramo dvitheeya-ghadana-aashrithamo nattellu-aashrithamo aakam. nattellu-swatantra rotamer librarikal nattellu roopeekaranathekkurichu paraamarsikkunnilla, koodaathe oru prathyeka tharatthilulla labhyamaya ellah side cheyinukalil ninnum kanakkakkunnu (udaaharanathinu, 1987 ll yelile chinthakarum richaardukalum cheytha oru rotamer libraryude aadya udaaharanam). dvitheeya-ghadana-ashrita librarikal formula _ 1-helix, formula _ 2-sheett allengil koyil dvitheeya gadanakalkkaayi vyathyastha dihedral konukalum/allengil rotamer aavruthikalum avatharippikkunnu. baakkbon-dependent rotamer librarikal dvitheeya ghadana pariganikkathe, baakkbon dihedral angle formula 3, formula 4 enniva nirvachichirikkunnathupo praadeshika baakkbon konformeshane aasrayichulla formationukalum/allengil freekwansikalum avatharippikkunnu.
mikka softweyarukalilum upayogikkunna eee librarikalude aadhunika pathippukal probability allengil freekwansiyude bahumukha vitharanangalayi avatharippikkunnu, avide kodumudikal listtukalile vyakthigatha rotamarukalaayi kanakkaakkappedunna dihedral-angle roopeekaranangalumaayi poruthappedunnu. chila pathippukal valare shradhaapoorvvam kyoorett cheytha daattaye adisthaanamaakkiyullathum praadhamikamaayi ghadana moolyanirnnayathinaayi upayogikkunnathum mattullava valare valia daatta settukalile aapekshika aavruthikalkku oonnal nalkukayum dunbrack rotamer librarikal polulla ghadana pravachanathinaayi praadhamikamaayi upayogikkunna roopavumaanu.
side cheyin packing reethikal proteininte hydrophobic coor vishakalanam cheiyunnathinu ettavum upayogapradamaanu, avide side cheyinukal kooduthal aduthu paaykk cheythirikkunnu; avaykku ayanja parimithikaleyum uparithala avashishtangalude uyarnna vazhakkatheyum abhisambodhana cheiyunnathil kooduthal budhimuttundu, ithu palappozhum onninekkaal onniladhikam rotamer roopeekaranangal ulkkollunnu.
quaternary ghadana.
rando athiladhikamo proteinukalude samuchayangalude kaaryatthil, proteinukalude gadanakal ariyappedukayo uyarnna krithyathayode pravachikkappedukayo cheiyunna saahacharyathil, protein-protein docking reethikal complexinte ghadana pravachikkaan upayogikkaam. samuchayathinte aduppathil nirddishta saittukalile mutationukalude swaadheenathekkurichulla vivarangal sankeernamaaya ghadana manasilakkaanum docking reethikale nayikkanum sahayikkunnu.
software.
protein ghadana pravachikkunnathinulla dhaaraalam software upakaranangal nilavilundu. homology modeling, protein threading, "abb initio" reethikal, dvitheeya ghadana pravachanam, transmembran helix, signal pepttaid pravachanam enniva sameepanagalil ulppedunnu. prathyekichum, protein homology kandethalinum deerghakaala hraswakaala memory adisthaanamaakkiyulla aazhathilulla patanam 2007 muthal eee aavashyathinaayi upayogikkunnu,
proteinukalude subsellular localisation pravachikkuka.
casp pareekshanangale adisthaanamaakkiyulla sameepakaala vijayakaramaya chila reethikalil aii-tasser, echechpred, alfafold enniva ulppedunnu. 2021ll, alfafold nilavil mikacha prakadanamaanu kaazhchavachathu.
oru proteininte ghadana ariyunnathu palappozhum pravarthanaparamaaya pravachanavum anuvadikkunnu. udaaharanathinu, kolajan deerghakaalamaayi vikasippichirikkunna fiber polulla shringalayilekku madakkikkalayukayum athu oru fiber proteinakkukayum cheiyunnu. aduthide, protein madakalum angane protein ghadanayum pravachikkaan niravadhi saankethikavidyakal vikasippicheduthittundu, udaaharanathinu, aitaasar, alfafold.
eiii. aii reethikal.
protein gadanakal pravachicha aadyathe aysukalilonnaanu alfafold. 2018ll nadanna 13-aamath casp malsarathil googilinte deep mind aanu ithu avatharippichathu. alfafold oru neural network sameepanathe aasrayikkunnu, ithu amino assid shreniyum allined homologous shrenikalum upayogichu oru nischitha proteinulla ellah hydrajan ithara aattangaludeyum 3D kordinettukal nerittu pravachikkunnu. aavarthichulla paalikaliloode inputtukal prosess cheiyunna oru trunk vyakthamaaya 3D ghadana avatharippikkunna oru structure module alfafold netvarkkil adangiyirikkunnu. protein ghadana pravachanathinaayi munbathe neural netvarkkukal ell. ezz. tii. emm upayogichirunnu.
alfafold protein kordinettukal nerittu outtputtu cheiyunnathinaal, protein shreniyude dairkhyathe aashrayich graphik prosessing yoonit (gpu) minitt muthal gpu manikkoor vare alfafold pravachanangal nadathunnu.
pravachicha protein gadanakalude nilavile iai reethikalum daattaabesukalum.
alfafold 2, casp 14 ll avatharippichu, koodaathe protein gadanakal ekadesham pareekshanathmaka krithyathayode pravachikkaan ithinu kazhiyum. alfafoldine athivegam rosettaafoldum pinneedu omegafold sm metagenomic atlasum pinthudarnnu. aduthide nadanna oru padanatthil, somer thudangiyavar. 2022ll genome vyaakhyaanathil protein ghadana pravachanatthinte prayogam pradharshippichu, prathyekichum kanakkukoottal pravachicha gadanakal upayogichu pravarthanakshamamaaya protein isophomukal thirichariyunnathil, ithu labhyamaan.isophome.aiyo. eee patanam oru genome vyaakhyaana upakaranamenna nilayil protein ghadana pravachanatthinte vaagdaanam eduthukaanikkukayum eathu genome vyaakhyaanavum vardhippikkaan upayogikkaavunna praayogikavum ghadana-maargganirddeshithavumaaya sameepanam avatharippikkukayum cheiyunnu.
europian bioinformatics instittyoottum deep mind chernnu pravachicha protein gadanakalkkaayi alfafold-ibi daattaabes nirmmichu.
automatic structure pravachana servarukalude vilayiruthal.
protein ghadana pravachanathinulla saankethikavidyakalude nirnaayaka vilayiruthaline soochippikkunna casp, 1994 muthal oro rund varshathilum nadakkunna protein ghadana pravachanathinaayulla oru community wide pareekshanamaanu. protein ghadana pravachanathinaayi (casp 7 ll avatharippicha server vibhaagam) labhyamaya manushya, automated allatha reethishaasthrathinteyum (manushya vibhaagam) automatic servarukaludeyum gunanilavaaram vilayiruthaan casp avasaram nalkunnu.
puthiya protein gadanakalkkaayi andhamaya pravachanangal upayogichu automated protein structure pravachana serverukale prathivaara adisthaanathil kyaami3dii thudarchayaaya automated model moolyanirnnaya server vilayiruthunnu. athidhi samgham athinte websaittil phalangal prasidheekarikkunnu.

