Structural Biochemistry/Protein Design

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Protein design is the design of new proteins, either from scratch or by making calculated variations of a known structure. There is hope that by designing lattice proteins, or highly simplified computer models of proteins that are used to investigate protein folding and secondary structural modification of real proteins, one can develop better applications in medication and bioengineering.

While the possible amino acid sequences are enormous, only a subset will fold reliably and quickly to a single native state. Protein design involves identifying these sequences through observing their free energy minimum, and the molecular interactions that stabilize proteins. Protein design can be accomplished using computer models, which are able to generate sequences that fold to the desired structure. Using computational methods, a protein with a novel fold—Top7[1], an artificial 93-residue protein—has been designed, as well as sensors for unnatural molecules. This is also referred to inverse folding as a tertiary structure is first specified, and then a sequence is identified which will fold to it.

Other small proteins that have been created include proteins result in chiroselective catalysis[2], ion detection[3], and antiviral behavior[4].

References[edit]

  1. 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, doi:10.1126/science.1089427, PMID 14631033 
  2. 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, http://www.nature.com/nature/journal/v409/n6822/abs/409797a0.html 
  3. Nagai, Takeharu; Sawano, Asako; Park, Eun Sun & Miyawaki, Atsushi (2001), "Circularly permuted green fluorescent proteins engineered to sense Ca2+", PNAS 98 (6): 3197–3202, doi:10.1073/pnas.051636098, PMID 11248055 
  4. Root, Michael J.; Kay, Michael S.; Kim, Peter S. (2001), "Protein design of an HIV-1 entry inhibitor", Science 291 (5505): 884–888, doi:10.1126/science.1057453, http://www.sciencemag.org/content/291/5505/884.abstract