Raka'a
1. Gabatarwa zuwa Haƙiƙa na Artificial a Chemistry: Matsayi, Iyakoki, Tabbatarwa da Da'a 2. Wakilin Kwayoyin Halitta da Tsarin Sinadarai: Tabbatarwa tare da SMILES, InChi da RDKit 3. Hasashen amsawa da injina: Samfur, yanayi da Hasashen Hasashen Mummuna 4. Taimakon Fassarar Bakan: NMR, IR da Mass Spectrometry 5. Bita na wallafe-wallafe da Tsare-tsaren Haɗa: Tushen, Tsari da Taswirar Hanya 6. Binciken Bayanai na Chemical da Python: pandas, Stoichiometry da Calibration 7. Hasashen Dukiyar Kwayoyin Halitta da QSAR: Ƙaddamarwa, pKa da Iyakan Model 8. Takardun dakin gwaje-gwaje: Littafin Bayanin Gwaji, ELN da Maimaituwa 9. Ƙimar Tsaro da Haɗari: GHS, SDS da Iyaka na Hankali na Artificial 10. Tabbatarwa, Hallucination, da Mutuncin Kimiyya 11. Dan Adam a Gwaji: Da'a, Keɓantawa, Nauyi da Ƙarshe-zuwa Ƙarshen Aiki
Naúrar 7 / 11

Hasashen Dukiyar Kwayoyin Halitta da QSAR: Ƙaddamarwa, pKa da Iyakan Model

Riba:

  • Ikon bambanta tsakanin fasalulluka masu ƙididdigewa da ƙididdige fasali da ƙididdige matakan amincewa
  • Ability don kimanta yankin da samfurin ya dogara ta hanyar amfani da ra'ayi na yankin aiki
  • Ƙarfin fahimtar cewa ya kamata mutum yayi amfani da tsinkayar dabi'a don ƙaddamar da 'yan takara kuma ya yanke shawara ta ƙarshe ta hanyar gwaji.

Kafin hada kwayoyin halitta, sau da yawa muna tambaya: "Shin yana da ruwa mai narkewa? Yaya acidic yake? Shin yana haye membrane? Shin yana da kyau a matsayin dan takarar magani?" Hasashen amsoshin waɗannan tambayoyin kafin gwajin yana adana lokaci mai yawa. AI da ƙwararrun ƙirar sa (musamman QSAR - Ƙwararrun Tsarin-Ayyukan Ayyuka, i.e. ƙididdigan ƙididdiga waɗanda ke tsinkayar dukiya daga masu siffanta tsarin kwayoyin halitta) suna da ƙarfi a cikin waɗannan tsinkaya. Amma waɗannan tsinkaya tsinkaya ce ta yuwuwar, ba ma'auni ba. A cikin wannan rukunin, za mu koyi game da hasashen fasali, ƙarfinsa da mafi mahimmancin ra'ayi, yankin aiki (yankin da ƙirar ke da aminci).

Wadanne siffofi aka annabta?

  • logP: Matsakaicin rabon mai / ruwa na kwayoyin; Yana nuna lipophilicity (son mai). Mahimmanci a cikin shaye-shayen ƙwayoyi.
  • Solubility (logS): Yadda yake narkewa cikin ruwa.
  • pKa: Acidity/alkaliness; pH wanda ƙungiyar ta ionizes.
  • TPSA: Topological polar surface area; Ana amfani da shi a cikin ƙididdige ƙididdiga.
  • Lipinski "mulkin biyar": Ƙofi masu dacewa don nauyin kwayoyin halitta, logP, adadin masu ba da gudummawar H-bond/masu yarda da 'yan takarar maganin baka.

Wasu daga cikin waɗannan ƙididdiga ana ƙididdige su ta hanyar ƙididdigewa (misali TPSA, lambobin H-bond) tare da kayan aiki kamar RDKit; Wasu daga cikinsu ƙididdiga ne na ƙididdiga (logS, ayyukan nazarin halittu). Sanin wannan bambance-bambance yana ƙayyade nawa kuka dogara.

Tukwici: Bambance ko fasalin “an ƙididdige shi” (tushen doka, maimaituwa) ko “annabta” (daga ƙirar, rashin tabbas). Yi babban kwarin gwiwa a cikin ƙididdiga, amincewa da hankali kan tsinkaya, kuma tabbatar da tsinkaya ta gwaji.

Iyakar aiki: mafi mahimmancin ra'ayi

Samfurin QSAR yana aiki da kyau akan kwayoyin halitta masu kama da kwayoyin da aka horar da su. Idan ka ba da kwayoyin halitta wanda ya bambanta da bayanan horo (misali, kwarangwal mai girma, wanda ba a saba ba), samfurin zai kasance yana samar da lamba, amma lambar ba za ta kasance abin dogara ba. Ana kiran wannan "kasancewa a waje da iyakokin aiki." Samfurin koyaushe yana ba da amsa; Aikin ku ne ku bayyana ko amsar abin dogaro ce ko a'a.

Yana da ma fi haɗari lokacin da ƙirar harshe ya ba da ƙimar sifa: yana samar da lambar a matsayin ƙimar "mai yiwuwa", ba tare da ƙididdigewa ba. Don haka idan zai yiwu, sami ƙimar fasali daga kayan aikin tantancewa (RDKit) ko ƙirar QSAR wanda ke ba da rashin tabbas, ba daga ƙirar harshe ba.

Mataki-mataki: tsinkayar fasali mai aminci

  1. Tabbatar da kwayoyin halitta: Fassara SMILES tare da RDKit (raka'a 2).
  2. Yi ƙididdige ƙididdigewa: MA, logP (ƙididdigewa), TPSA, lambobin haɗin H daga RDKit.
  3. Alama tsinkaya daban: Ajiye tsinkayar ƙira kamar logS, ayyuka, da sauransu tare da alamar "hasashen".
  4. Bincika yankin da za a iya amfani da su: Shin kwayoyin halitta sunyi kama da bayanan horo? Shin yana da girma sosai/na saba?
  5. Yi amfani da matsayi, ba yanke shawara ba: Yi amfani da tsinkaya don tantance 'yan takara; Babban zabi shine gwaji.
  6. Rufe ta gwaji: Tabbatar da kaddarorin masu mahimmanci (slubility, pKa) ta aunawa.

Samfura huɗu masu kwafi

1) Ƙaddara fasali tare da RDKit:

daga rdkit shigo da Chemfrom rdkit.Chem import Descriptors, rdMolDescriptorsmol = Chem.MolFromSmiles("CC(=O)Oc1ccccc1C(=O)O") # aspirinprint("MA:", zagaye(Descriptors.MolWt(mol),2))buga("):logP (calculated) zagaye (Descriptors.MolLogP (mol),2)) buga ("TPSA:", zagaye (Descriptors.TPSA(mol),1)) buga ("H-bond donor:", rdMolDescriptors.CalcNumHBD(mol)) buga ("H-bond karba:", rdMolDescriptors.CalcNumHBA(mol)

2) Ƙimar dokokin Lipinski:

Molecule (SMILES): [SMILES] Aiki: Ƙimar yarda da ka'idar Lipinski na biyar tare da MA, logP, HBD, HBA ƙididdiga daga RDKit. Alama kowane ma'auni daban azaman wucewa/ gazawa. Dokar: KADA KA sanya lambobi; Zan samu daga RDKit, ku yi sharhi.

3) Ƙimar fasali + buƙatar rashin tabbas:

Molecule (SMILES): [SMILES] Aiki: Ba da ƙididdige ƙididdige ƙimar ruwa mai narkewa (logS) (babba/matsakaici/ƙananan) da bayyana ma'anar tare da fasali na tsari. Kar a bada ainihin lamba; Faɗa cewa wannan HAKIKA ne kuma yana buƙatar tabbatarwa ta gwaji. Gargaɗi idan kwayar halitta tana da sabon tsari (haɗarin aiki).

4) Matsayin ɗan takara (fifi ba da fifiko ta tsinkaya):

Da ke ƙasa akwai MURMUSHI na kwayoyin 5. Aiki: Sanya su cikin sharuddan ruwa mai narkewa (mafi soluble zuwa ƙarami) bisa tsarin fasali (yawan ƙungiyoyin polar, zobe, lipophilicity) .Rubuta barata ga kowane yanke shawara. Lura: Wannan nau'in FARKO ne; Za a yi zaɓi na ƙarshe ta hanyar aunawa.

Rauni mai ƙarfi / Ƙarfi mai ƙarfi

Rauni:

Menene narkewar wannan kwayar halitta?

AI yana samar da lambar da ba ta wanzu a ƙarƙashin lissafin (misali "12 mg / ml"); Yana ba da tabbaci amma yana iya zama kuskure.

Mai ƙarfi:

Molecule (SMILES): [SMILES].Aiki: 1) Zan ba logP, TPSA, HBD/HBA da za a lissafta tare da RDKit: [daraja].2) Dangane da waɗannan dabi'u, fassara ko ƙuduri yana da girma / matsakaici / low.3) Ba da lambar daidai; Bayyana cewa zato ne kuma ana buƙatar gwaji.

Bambanci: mun ɗauki ƙimar ƙididdiga daga abin hawa kuma muka sanya AI kawai ta fassara su; Mun nemi rashin tabbas a sarari da buƙatar gwaji.

Nau'in fasali da matakin amincewa

fasali

Yadda ake samu

amana

bayanin kula

nauyin kwayoyin halitta

RDKit (ƙaddara)

mai girma

Yanke daga dabarar

TPSA, HBD/HBA

RDKit (ƙaddara)

babba

bisa mulki

logP (ƙididdigewa)

Samfurin RDKit

matsakaici-high

Maiyuwa ya karkata daga gwaji

logS (ƙuduri)

Ƙimar QSAR

matsakaici

Ya dogara da yankin da ake amfani da shi

pKa

samfuri na musamman

matsakaici

Ya fada cikin hadadden tsari

nazarin halittu aiki

QSAR/ML

Mai canzawa

Tabbatar gwadawa da tabbatarwa

kananan lokuta

Case 1 - Adadin shawarwari da aka dace. Wani dalibi ya tambayi AI game da solubility na fili; Ya karɓi amsar "25 mg / ml" kuma ya kafa ƙirar gwaji daidai. Ainihin ƙimar a cikin ma'aunin shine ~ 2 mg/mL, bambanci mai ninki 10. AI ta sanya lambar. Darasi: kar a ɗauki kaddarori kamar ƙuduri azaman lambobi daga ƙirar harshe; Hasashen inganci + ma'auni.

Case 2 - A waje da ikon yin aiki. Wani samfurin QSAR ya ce "aikin yana da girma" don babban macromolecule wanda ya bambanta da tsarin horo. Mai amfani ya lura cewa kwayar halitta ba ta yi kama da bayanan horo ba kuma ya yi la'akari da tsinkaya marar dogara; Gwajin ya ba da ƙarancin aiki sosai. Darasi: samfurin koyaushe yana amsawa; Idan ba ta da iyaka, amsar ba ta da amfani.

Case 3 - Daidaita amfani da Lipinski. A kan kwayoyin dan takarar guda daya, AI ya kimanta Lipinski tare da dabi'u daga RDKit: MA 512 (> 500, iyakar iyaka), logP 4.8 (mafi kyau), HBD 2, HBA 7. Mai amfani ya fassara daidai "ma'auni daya ya rage amma ka'idar ba cikakke ba ce" kuma bai kawar da kwayoyin gaba daya ba. Darasi: dokoki jagorori ne, ba ƙofa ba; Fassara tare da mahallin.

Kuskuren gama gari

  • Samun ƙidaya fasalin daga ƙirar harshe. Ƙimar da ba a lissafta an ƙirƙira su ne; Yi amfani da ƙayyadaddun kayan aiki ko samfuri tare da rashin tabbas.
  • Yin watsi da filin aiki. Samfurin yana haifar da lambobi don kowane kwayoyin halitta; m waje filin.
  • Yin la'akari da ƙididdige ma'auni. logS shine kimantawa; Ba madadin ƙudurin gwaji ba.
  • Yin la'akari da Lipinski cikakkiyar doka. Ba a kawar da dan takarar da ke kan iyakar kai tsaye ba; Magunguna da yawa sun keta doka.
  • Rikita "ƙididdige" tare da "ƙimantawa." Ana ƙididdige TPSA (abin dogaro), ana ƙididdige ayyukan (rashin tabbas).
Tsanaki: Hasashen fasali yana da kyau ga matsayi da ba da fifiko ga 'yan takara; amma ba don yanke shawara kadai ba. "The model said soluble" shi ne hasashe; "Na auna, ya narke" sakamako ne.

A takaice

  • Za'a iya hasashen kaddarorin kwayoyin halitta kafin gwajin kuma yana adana lokaci mai yawa.
  • Wasu fasalulluka ana ƙididdige su da ƙididdigewa (MA, TPSA, HBD/HBA), wasu ƙididdiga ne na ƙididdiga (logS, ayyuka).
  • Yankin zartarwa shine mafi mahimmancin ra'ayi: samfurin koyaushe yana amsawa, amma ba abin dogaro bane a wajen yankin.
  • Sami ƙididdige fasalin daga RDKit ko ƙirar rashin fahimta, ba ƙirar harshe ba.
  • Yi amfani da tsinkaya don tantance 'yan takara; Yi yanke shawara ta ƙarshe ta gwaji.

Aikin aikace-aikace

Zaɓi kwayoyin halitta guda biyar (misali jerin magunguna). Yi lissafin MA, logP, TPSA, HBD, HBA ga kowanne tare da RDKit kuma kimanta Lipinski. Na dabam, tambayi AI don ƙididdige ƙididdiga (ba lamba) na solubility na kowane kwayoyin halitta da filin gargadin aiwatarwa. Tattara ƙididdiga masu ƙima da tsinkayar AI a cikin tebur. Wanne kwayoyin halitta ya ba da bayanin martaba mai kama da ƙwayoyi? Ina rashin tabbas ya fi girma?

jerin abubuwan dubawa

  • [ ] Na bambanta tsakanin ƙayyadaddun ƙididdiga da kaddarorin annabta.
  • [ ] Ina samun ƙimar kadarorin daga RDKit/samfurin, ba ƙirar harshe ba.
  • [ ] Na lura da kwayoyin halitta a waje da iyakokin aiki.
  • [ ] Ina amfani da Lipinski a matsayin jagora, ba cikakkiyar doka ba.
  • [ ] Ina amfani da tsinkaya don matsayi da yanke shawara don gwaji.
  • [ ] Ina da shiri don tabbatar da mahimman abubuwa ta hanyar aunawa.
A baya Na gaba