Protein design
From Wikipedia, the free encyclopedia
Protein design is the design of new protein molecules from scratch. The number of possible amino acid sequences is infinite, but only a subset of these sequences will fold reliably and quickly to a single native state. Protein design involves identifying such sequences, in particular those with a physiologically active native state.
Protein design requires an understanding of the process by which proteins fold. In a sense it is the reverse of structure prediction: a tertiary structure is specified, and a primary sequence is identified which will fold to it. The protein folding process is still not completely understood, although recent developments in both experiment and theory have revealed much new information.
The design of minimalist computer models of proteins (lattice proteins), and the secondary structural modification of real proteins, began in the mid-1990s. The de novo design of real proteins became possibly shortly afterwards, and the 21st century has seen the creation of small proteins with real biological function including catalysis and antiviral behaviour. There is great hope that the design of these and larger proteins will have application in medicine and bioengineering.
Computational protein design algorithms seek to identify amino acid sequences that have low energies for target structures. While the sequence-conformation space that needs to be searched is large, the most challenging requirement for computational protein design is a fast, yet accurate, energy function that can distinguish optimal sequences from similar suboptimal ones. Using computational methods, a protein with a novel fold has been designed[1], as well as sensors for un-natural molecules[2].
[edit] Software
EGAD: A Genetic Algorithm for protein Design[3]. A free, open-source software package for protein design and prediction of mutation effects on protein folding stabilities and binding affinities. EGAD can also consider multiple structures simultaneously for designing specific binding proteins or locking proteins into specific conformational states. In addition to natural protein residues, EGAD can also consider free-moving ligands with or without rotatable bonds. EGAD can be used with single or multiple processors.
[edit] References
- Jin et al, Structure, 11, 581 (2003).
- Nagai et al, Proc. Natl. Acad. Sci. USA, 98, 3197 (2001).
- Saghatelian et al, Nature, 409, 797 (2001).
- Kuhlman et al "Science", 302:1364 (2003)[4]
- Looger et al "Nature", 423:185 (2003)[5]
- Pokala and Handel "J Mol Biol", 347:203 (2005)[6]
