Protein sequence randomization: efficient estimation of protein stability using knowledge-based potentials

Markus Wiederstein, Manfred J. Sippl

    Research output: Contribution to journalArticle

    Abstract

    Modifications of the amino acid sequence generally affect protein stability. Here, we use knowledge-based potentials to estimate the stability of protein structures under sequence variation. Calculations on a variety of protein scaffolds result in a clear distinction of known mutable regions from arbitrarily chosen control patches. For example, randomly changing the sequence of an antibody paratope yields a significantly lower number of destabilized mutants as compared to the randomization of comparable regions on the protein surface. The technique is computationally efficient and can be used to screen protein structures for regions that are amenable to molecular tinkering by preserving the stability of the mutated proteins.

    Translated title of the contributionProtein Sequence Randomization: Efficient Estimation of Protein Stability Using Knowledge-Based Potentials
    Original languageEnglish
    Pages (from-to)1199-1212
    Number of pages13
    JournalJournal of Molecular Biology
    Volume345
    Issue number5
    DOIs
    Publication statusPublished - 4 Feb 2005

    Bibliographical note

    345

    Fields of Science and Technology Classification 2012

    • 106 Biology

    Keywords

    • Amino Acid Sequence
    • Computational Biology
    • Models, Molecular
    • Mutation/genetics
    • Proline/analysis
    • Protein Denaturation
    • Protein Engineering
    • Protein Structure, Tertiary
    • Proteins/chemistry
    • Random Allocation
    • Thermodynamics

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