Format

Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9594-7. doi: 10.1073/pnas.0800938105. Epub 2008 Jul 8.

Bioinformatic method for protein thermal stabilization by structural entropy optimization.

Author information

  • 1Departments of Biochemistry and Computer Science, University of Wisconsin, Madison, WI 53706, USA.

Abstract

Engineering proteins for higher thermal stability is an important and difficult challenge. We describe a bioinformatic method incorporating sequence alignments to redesign proteins to be more stable through optimization of local structural entropy. Using this method, improved configurational entropy (ICE), we were able to design more stable variants of a mesophilic adenylate kinase with only the sequence information of one psychrophilic homologue. The redesigned proteins display considerable increases in their thermal stabilities while still retaining catalytic activity. ICE does not require a three-dimensional structure or a large number of homologous sequences, indicating a broad applicability of this method. Our results also highlight the importance of entropy in the stability of protein structures.

PMID:
18621726
[PubMed - indexed for MEDLINE]
PMCID:
PMC2474475
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk