Tolerance of different proteins for amino acid diversity

Motoshi Suzuki, Fred C. Christians, Baek Kim, Adonis Skandalis, Margaret E. Black, Lawrence A. Loeb

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Random mutagenesis of genes followed by positive genetic selection in bacteria requires that the variant molecules confer biological activity, and is thus the most demanding approach for generating new functionally active molecules. Furthermore, one can learn much about the protein in question by comparing the population of selected molecules to the library from which they were selected. Described here is a mathematical method designed to guide such comparisons. We use as examples the results of randomization-selection studies of four different proteins. There exists, in general, a positive correlation between the number of amino acid substitutions in a critical region of a protein and the likelihood of inactivation of that protein; a correlation long suspected, but developed here in detail. At this time, we are comparing regions in different proteins and our conclusions must be limited. However, the method presented can serve as a guideline for anticipating the yield of new active mutants in genetic complementation assays based on the extent of randomization.

Original languageEnglish
Pages (from-to)111-118
Number of pages8
JournalMolecular Diversity
Volume2
Issue number1-2
DOIs
Publication statusPublished - 01-01-1996
Externally publishedYes

Fingerprint

amino acids
Amino acids
proteins
Proteins
Amino Acids
Random Allocation
Molecules
mutagenesis
molecules
Mutagenesis
Genetic Selection
Amino Acid Substitution
activity (biology)
Bioactivity
genes
deactivation
bacteria
Libraries
Assays
Bacteria

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Information Systems
  • Molecular Biology
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Suzuki, M., Christians, F. C., Kim, B., Skandalis, A., Black, M. E., & Loeb, L. A. (1996). Tolerance of different proteins for amino acid diversity. Molecular Diversity, 2(1-2), 111-118. https://doi.org/10.1007/BF01718708
Suzuki, Motoshi ; Christians, Fred C. ; Kim, Baek ; Skandalis, Adonis ; Black, Margaret E. ; Loeb, Lawrence A. / Tolerance of different proteins for amino acid diversity. In: Molecular Diversity. 1996 ; Vol. 2, No. 1-2. pp. 111-118.
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Suzuki, M, Christians, FC, Kim, B, Skandalis, A, Black, ME & Loeb, LA 1996, 'Tolerance of different proteins for amino acid diversity', Molecular Diversity, vol. 2, no. 1-2, pp. 111-118. https://doi.org/10.1007/BF01718708

Tolerance of different proteins for amino acid diversity. / Suzuki, Motoshi; Christians, Fred C.; Kim, Baek; Skandalis, Adonis; Black, Margaret E.; Loeb, Lawrence A.

In: Molecular Diversity, Vol. 2, No. 1-2, 01.01.1996, p. 111-118.

Research output: Contribution to journalArticle

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Suzuki M, Christians FC, Kim B, Skandalis A, Black ME, Loeb LA. Tolerance of different proteins for amino acid diversity. Molecular Diversity. 1996 Jan 1;2(1-2):111-118. https://doi.org/10.1007/BF01718708