Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (129K) 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 (6)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Jensen, L. J.
Right arrow Articles by Kretzschmar, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jensen, L. J.
Right arrow Articles by Kretzschmar, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, Vol 26, Issue 3 697-702, Copyright © 1998 by Oxford University Press

ARTICLES

Scoring functions for computational algorithms applicable to the design of spiked oligonucleotides

LJ Jensen, KV Andersen, A Svendsen and T Kretzschmar
Department of Enzyme Design, Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark.

Protein engineering by inserting stretches of random DNA sequences into target genes in combination with adequate screening or selection methods is a versatile technique to elucidate and improve protein functions. Established compounds for generating semi-random DNA sequences are spiked oligonucleotides which are synthesised by interspersing wild type (wt) nucleotides of the target sequence with certain amounts of other nucleotides. Directed spiking strategies reduce the complexity of a library to a manageable format compared with completely random libraries. Computational algorithms render feasible the calculation of appropriate nucleotide mixtures to encode specified amino acid subpopulations. The crucial element in the ranking of spiked codons generated during an iterative algorithm is the scoring function. In this report three scoring functions are analysed: the sum-of-square- differences function s, a modified cubic function c, and a scoring function m derived from maximum likelihood considerations. The impact of these scoring functions on calculated amino acid distributions is demonstrated by an example of mutagenising a domain surrounding the active site serine of subtilisin-like proteases. At default weight settings of one for each amino acid, the new scoring function m is superior to functions s and c in finding matches to a given amino acid population.
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
 Nucleic Acids ResHome page
R. A. Craig, J. Lu, J. Luo, L. Shi, and L. Liao
Optimizing nucleotide sequence ensembles for combinatorial protein libraries using a genetic algorithm
Nucleic Acids Res., November 4, 2009; (2009) gkp906v1.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
A. Hidalgo, A. Schliessmann, R. Molina, J. Hermoso, and U. T. Bornscheuer
A one-pot, simple methodology for cassette randomisation and recombination for focused directed evolution
Protein Eng. Des. Sel., September 1, 2008; 21(9): 567 - 576.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. J. Volles and P. T. Lansbury Jr
A computer program for the estimation of protein and nucleic acid sequence diversity in random point mutagenesis libraries
Nucleic Acids Res., June 29, 2005; 33(11): 3667 - 3677.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
W. Wang and J. G. Saven
Designing gene libraries from protein profiles for combinatorial protein experiments
Nucleic Acids Res., November 1, 2002; 30(21): e120 - e120.
[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.