Fluorine NMR studies of a protein containing fluorinated arnino acid analogs can often be used to probe structure and dynamics as well as conformational changes produced by binding of small molecules. The relevance of fluorine NMR results obtained with these systems to the properties of the corresponding native (non-fluorinated) proteins depends upon the extent to which protein structure and dynamics are altered by the presence of fluorine. The present work uses molecular dynamics simulations to explore effects of replacement of tryptophan by 6-fluorotryptophan in folate and methotrexate complexes of the enzyme dihydrofolate reductase (DHFR). Simulations of the foiate-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 over the time-scale of 100 ps. Calculations with the metho-trexate-enzyme complex predict dynamical behavior of the protein similar to that of the folate complex for both the fluorinated and native enzyme. It appears that substitution of 6-fluorotryptophan for tryptophan has little effect on either structures or dynamics of DHFR in these complexes. (This work was supported in part by NIH Grant GM 25975 and the UCSB CoR.).
|Original language||English (US)|
|State||Published - 1997|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology