The Effects of p-Azidophenylalanine Incorporation on Protein Structure and Stability
| Autor: | Kristen M. Wilding, Bradley C. Bundy, Addison K. Smith, Joshua W. Wilkerson, Thomas A. Knotts |
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| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
010304 chemical physics General Chemical Engineering General Chemistry Protein engineering Library and Information Sciences 01 natural sciences 0104 chemical sciences Computer Science Applications Amino acid 010404 medicinal & biomolecular chemistry Residue (chemistry) Molecular dynamics Protein stability Protein structure chemistry 0103 physical sciences Biophysics P-azidophenylalanine |
| Zdroj: | Journal of Chemical Information and Modeling. 60:5117-5125 |
| ISSN: | 1549-960X 1549-9596 |
| DOI: | 10.1021/acs.jcim.0c00725 |
| Popis: | Functionalization is often needed to harness the power of proteins for beneficial use but can cause losses to stability and/or activity. State of the art methods to limit these deleterious effects accomplish this by substituting an amino acid in the wild-type molecule into an unnatural amino acid (uAA), such as p-azidophenylalanine (pAz), but selecting the residue for substitution a priori remains an elusive goal of protein engineering. The results of this work indicate that all-atom molecular dynamics simulation can be used to determine whether substituting pAz for a natural amino acid will be detrimental to experimentally-determined protein stability. These results offer significant hope that local deviations from wild-type structure caused by pAz incorporation observed in simulations can be a predictive metric used to reduce the number of costly experiments that must be done to find active proteins upon substitution withpAz and subsequent functionalization. |
| Databáze: | OpenAIRE |
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