Bioinformatics Advance Access published online on August 22, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn450
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Optimal Design of Thermally Stable Proteins


1Department of Computer Science, University of Wisconsin-Madison, 1210 W. Dayton, Madison, WI 53706
2Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706
3Department of Mathematics, University of Wisconsin-Madison, 480 Lincoln Drive, Madison, WI 53706
*To whom correspondence should be addressed. Dr. Julie C. Mitchell, E-mail: mitchell{at}biochem.wisc.edu
| Abstract |
|---|
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 non-negative weights and is solved efficiently using Dijkstra's method.
These authors contributed equally to this work
Associate Editor: Prof. Burkhard Rost
Received on May 16, 2008; revised on July 29, 2008; accepted on August 19, 2008