Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (61)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Topham, C. M.
Right arrow Articles by Blundell, T. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Topham, C. M.
Right arrow Articles by Blundell, T. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Protein Engineering, Vol 10, 7-21, Copyright © 1997 by Oxford University Press

ARTICLES

Prediction of the stability of protein mutants based on structural environment-dependent amino acid substitution and propensity tables

CM Topham, N Srinivasan and TL Blundell
Department of Crystallography, Birkbeck College, University of London, UK.

An approach to the prediction of mutant stability is described using knowledge of amino acid replacements that are tolerated within the families of homologous proteins of known 3-D structure. Amino acid variations in families of homologous proteins are converted to propensity and substitution tables; these provide quantitative information about the existence of an amino acid in a structural environment and the probability of replacement by any other amino acid. The tables are used to calculate a 'stability difference score', analogous to the difference in free energy between a mutant and the wild type. The method has been developed and tested using the high- resolution structures for T4 lysozyme and 159 site-specific mutants. We show that differences in stability scores are correlated with experimentally observed free energy differences and differences in melting temperature. Blind tests, using only structural information derived from the parent wild-type crystal structures, on a combined set of 83 staphylococcal nuclease and 68 barnase mutants showed a correlation of 0.80 in the predicted stability changes with experimental thermodynamic data. Approximately 86% of the predictions were correctly classified as destabilizing or stabilizing.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
K. Nagpal, T. S. Plantinga, J. Wong, B. G. Monks, N. J. Gay, M. G. Netea, K. A. Fitzgerald, and D. T. Golenbock
A TIR Domain Variant of MyD88 Adapter-like (Mal)/TIRAP Results in Loss of MyD88 Binding and Reduced TLR2/TLR4 Signaling
J. Biol. Chem., September 18, 2009; 284(38): 25742 - 25748.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
M. Masso and I. I. Vaisman
Accurate prediction of stability changes in protein mutants by combining machine learning with structure based computational mutagenesis
Bioinformatics, September 15, 2008; 24(18): 2002 - 2009.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. J. Ferguson, C. Alexander, S. W. Rossi, I. Liiv, A. Rebane, C. L. Worth, J. Wong, M. Laan, P. Peterson, E. J. Jenkinson, et al.
AIRE's CARD Revealed, a New Structure for Central Tolerance Provokes Transcriptional Plasticity
J. Biol. Chem., January 18, 2008; 283(3): 1723 - 1731.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
B. Shen, J. Bai, and M. Vihinen
Physicochemical feature-based classification of amino acid mutations
Protein Eng. Des. Sel., January 1, 2008; 21(1): 37 - 44.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
C. Deutsch and B. Krishnamoorthy
Four-Body Scoring Function for Mutagenesis
Bioinformatics, November 15, 2007; 23(22): 3009 - 3015.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
V. Parthiban, M. M. Gromiha, and D. Schomburg
CUPSAT: prediction of protein stability upon point mutations.
Nucleic Acids Res., July 1, 2006; 34(Web Server issue): W239 - W242.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
G. E. Crooks, R. E. Green, and S. E. Brenner
Pairwise alignment incorporating dipeptide covariation
Bioinformatics, October 1, 2005; 21(19): 3704 - 3710.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
G. E. Crooks and S. E. Brenner
An alternative model of amino acid replacement
Bioinformatics, April 1, 2005; 21(7): 975 - 980.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
B. Shen and M. Vihinen
Conservation and covariance in PH domain sequences: physicochemical profile and information theoretical analysis of XLA-causing mutations in the Btk PH domain
Protein Eng. Des. Sel., March 1, 2004; 17(3): 267 - 276.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
N. Boutonnet, W. Janssens, C. Boutton, J.-L. Verschelde, L. Heyndrickx, E. Beirnaert, G. van der Groen, and I. Lasters
Comparison of Predicted Scaffold-Compatible Sequence Variation in the Triple-Hairpin Structure of Human Immunodeficiency Virus Type 1 gp41 with Patient Data
J. Virol., June 27, 2002; 76(15): 7595 - 7606.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
S. I. Rogov and A. N. Nekrasov
A numerical measure of amino acid residues similarity based on the analysis of their surroundings in natural protein sequences
Protein Eng. Des. Sel., July 1, 2001; 14(7): 459 - 463.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
D. Gilis and M. Rooman
PoPMuSiC, an algorithm for predicting protein mutant stability changes. Application to prion proteins
Protein Eng. Des. Sel., December 1, 2000; 13(12): 849 - 856.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
K. Takano, M. Ota, K. Ogasahara, Y. Yamagata, K. Nishikawa, and K. Yutani
Experimental verification of the `stability profile of mutant protein' (SPMP) data using mutant human lysozymes
Protein Eng. Des. Sel., August 1, 1999; 12(8): 663 - 672.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
M.M. Gromiha, M. Oobatake, H. Kono, H. Uedaira, and A. Sarai
Role of structural and sequence information in the prediction of protein stability changes: comparison between buried and partially buried mutations
Protein Eng. Des. Sel., July 1, 1999; 12(7): 549 - 555.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.