Structural Biochemistry/Protein Design

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—Top7Kuhlman Brian Dantas Gautam Ireton Gregory C. Varani Gabriele Stoddard Barry L. Baker David yes 2003 Design of a Novel Globular Protein Fold with Atomic-Level Accuracy Science 14631033 302 5649 1364–1368 10.1126/science.1089427 , 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 catalysisSaghatelian Alan Yokobayashi Yohei Soltani Kathy Ghadiri M. Reza yes 2001 A chiroselective peptide replicator Nature 409 6822 797–801 10.1038/35057238 11236988 http://www.nature.com/nature/journal/v409/n6822/abs/409797a0.html, ion detectionNagai Takeharu Sawano Asako Park Eun Sun Miyawaki Atsushi yes 2001 Circularly permuted green fluorescent proteins engineered to sense Ca2+ PNAS 11248055 98 6 30630 3197–3202 10.1073/pnas.051636098 , and antiviral behaviorRoot Michael J. Kay Michael S. Kim Peter S. 2001 Protein design of an HIV-1 entry inhibitor Science 291 5505 884–888 10.1126/science.1057453 http://www.sciencemag.org/content/291/5505/884.abstract. References