Bioinformatics Advance Access originally published online on August 22, 2008
Bioinformatics 2008 24(20):2339-2343; doi:10.1093/bioinformatics/btn450
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Optimal design of thermally stable proteins


1Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, 2Department of Computer Science, University of Wisconsin-Madison, 1210 W. Dayton and 3Department of Mathematics, University of Wisconsin-Madison, 480 Lincoln Drive, Madison, WI 53706, USA
*To whom correspondence should be addressed.
| Abstract |
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Motivation: For many biotechnological purposes, it is desirable to redesign proteins to be more structurally and functionally stable at higher temperatures. For example, chemical reactions are intrinsically faster at higher temperatures, so using enzymes that are stable at higher temperatures would lead to more efficient industrial processes. We describe an innovative and computationally efficient method called Improved Configurational Entropy (ICE), which can be used to redesign a protein to be more thermally stable (i.e. stable at high temperatures). This can be accomplished by systematically modifying the amino acid sequence via local structural entropy (LSE) minimization. The minimization problem is modeled as a shortest path problem in an acyclic graph with nonnegative weights and is solved efficiently using Dijkstra's method.
Contact: mitchell{at}biochem.wisc.edu
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
Associate Editor: Burkhard Rost
Received on May 16, 2008; revised on July 29, 2008; accepted on August 19, 2008