Fluorine NMR experiments with a protein containing fluorinated amino acid analogs can often be used to probe structure and dynamics of the protein as well as conformational changes produced by binding of small molecules. The relevance of NMR experiments with fluorine-containing materials to characteristics of the corresponding native (nonfluorinated) proteins depends upon the extent to which these characteristics are altered by the presence of fluorine. The present work uses molecular dynamics simulations to explore the effects of replacement of tryptophan by 6-fluorotryptophan in folate and methotrexate complexes of the enzyme dihydrofolate reductase (DHFR) (Escherichia coli). Simulations of the folate-native enzyme complex produce local correlation times and order parameters that are generally in good agreement with experimental values. Simulations of the corresponding fluorotryptophan-containing system indicate that the structure and dynamics of this complex are scarcely changed by the presence of fluorinated amino acids. Calculations with the pharmacologically important methotrexate-enzyme complex predict dynamical behavior of the protein similar to that of the folate complex for both the fluorinated and native enzyme. It thus appears that, on the time scale sampled by these computer simulations, substitution of 6-fluorotryptophan for tryptophan has little effect on either the structures or dynamics of DHFR in these complexes.
|Original language||English (US)|
|Number of pages||14|
|State||Published - Sep 1997|
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