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Dizajn proteina

Dizajn proteina je proces formiranja novih proteina, bilo de novo ili putem pravljenja proračunatih varijacija poznatih struktura. Upotreba tehnika racionalnog dizajna je glavni aspekt proteinskog inženjerstva.

Dizajn računarskih modela proteina, i sekundarne strukturne modifikacije realnih proteina su počeli sredinom 1990-tih. De novo dizajn realnih proteina je postao moguć uskoro nakon toga, i u 21. veku je to postalo produktivno naučno polje.

Primeri dezajna proteina uredi

U ranom 21. veku je počeo razvoj malih proteina sa realnim biološkim funkcijama, uključujući stereoselektivnu katalizu,[1] detekciju jona,[2] i antiviralno dejstvo.[3] Koristeći računarske metode, protein sa novim strukturnim motivom je dizajniran, koji se naziva Top7,[4] kao i senzori za veštačke molekule.[5] Dizajn fuzionih proteina je proizveo rilonacept, lek koji je FDA odobrila za lečenje kriopirin vezanog periodičnog sindroma. Uz pomoć računarskog redizajna bilo je moguće promeniti specifičnot kofaktora Candida boidinii ksilozne reduktaze od NADPH u NADH.[6]

Reference uredi

  1. ↑ Saghatelian, Alan; Yokobayashi, Yohei; Soltani, Kathy & Ghadiri, M. Reza (2001). „A chiroselective peptide replicator”. Nature 409 (6822): 797–801. DOI:10.1038/35057238. PMID 11236988. 
  2. ↑ Nagai, Takeharu; Sawano, Asako; Park, Eun Sun & Miyawaki, Atsushi (2001). „Circularly permuted green fluorescent proteins engineered to sense Ca2+”. Proceedings of the National Academy of Sciences 98 (6): 3197–3202. Bibcode 2001PNAS...98.3197N. DOI:10.1073/pnas.051636098. PMC 30630. PMID 11248055. 
  3. ↑ Root, Michael J.; Kay, Michael S.; Kim, Peter S. (2001). „Protein design of an HIV-1 entry inhibitor”. Science 291 (5505): 884–888. Bibcode 2001Sci...291..884R. DOI:10.1126/science.1057453. 
  4. ↑ Kuhlman, Brian; Dantas, Gautam; Ireton, Gregory C.; Varani, Gabriele; Stoddard, Barry L. & Baker, David (2003). „Design of a Novel Globular Protein Fold with Atomic-Level Accuracy”. Science 302 (5649): 1364–1368. Bibcode 2003Sci...302.1364K. DOI:10.1126/science.1089427. PMID 14631033. 
  5. ↑ Looger, Loren L.; Dwyer, Mary A.; Smith, James J. & Hellinga, Homme W. (2003). „Computational design of receptor and sensor proteins with novel functions”. Nature 423 (6936): 185–190. Bibcode 2003Natur.423..185L. DOI:10.1038/nature01556. PMID 12736688. 
  6. ↑ Khoury, GA; Fazelinia, H; Chin, JW; Pantazes, RJ; Cirino, PC; Maranas, CD (October 2009). „Computational design of Candida boidinii xylose reductase for altered cofactor specificity”. Protein Science 18 (10): 2125–38. DOI:10.1002/pro.227. PMC 2786976. PMID 19693930. 

Literatura uredi

  • Dahiyat, Bassil I. & Mayo, Stephen L. (1997), „De Novo Protein Design: Fully Automated Sequence Selection”, Science 278 (5335): 82–87, DOI:10.1126/science.278.5335.82, PMID 9311930 
  • Sander, Chris; Vriend, Gerrit; Bazan, Fernando; et al., Amnon; Nakamura, Haruki; Ribas, Luis; Finkelstein, Alexei V.; Lockhart, Andrew i dr.. (1992), „Protein Design on computers. Five new proteins: Shpilka, Grendel, Fingerclasp, Leather and Aida”, Proteins: Structure, Function, and Bioinformatics 12 (2): 105–110, DOI:10.1002/prot.340120203, PMID 1603799 
  • Jin, Wenzhen; Kambara, Ohki; Sasakawa, Hiroaki; Tamura, Atsuo & Takada, Shoji (2003), „De Novo Design of Foldable Proteins with Smooth Folding Funnel: Automated Negative Design and Experimental Verification”, Structure 11 (5): 581–590, DOI:10.1016/S0969-2126(03)00075-3, PMID 12737823 
  • Pokala, Tracy M. & Handel, Navin (2005), „Energy Functions for Protein Design: Adjustment with Protein–Protein Complex Affinities, Models for the Unfolded State, and Negative Design of Solubility and Specificity”, Journal of Molecular Biology 347 (1): 203–227, DOI:10.1016/j.jmb.2004.12.019, PMID 15733929 
  • Röthlisberger, Daniela; Khersonsky, Olga; Wollacott, Andrew M.; Jiang, Lin; Dechancie, Jason; Betker, Jamie; Gallaher, Jasmine L.; Althoff, Eric A. i dr.. (2008), „Kemp elimination catalysts by computational enzyme design”, Nature 453 (7192): 190, Bibcode 2008Natur.453..190R, DOI:10.1038/nature06879, PMID 18354394 
  • Jiang, Lin; Althoff, Eric A.; Clemente, Fernando R.; Doyle, Lindsey; Rothlisberger, Daniela; Zanghellini, Alexandre; Gallaher, Jasmine L.; Betker, Jamie L. i dr.. (2008), „De Novo Computational Design of Retro-Aldol Enzymes”, Science 319 (5868): 1387, Bibcode 2008Sci...319.1387J, DOI:10.1126/science.1152692, PMID 18323453 

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