A molecular dynamics study of acylphosphatase in aggregation-promoting conditions: the influence of trifluoroethanol/water solvent.
The 98-residue protein acylphosphatase exhibits a high propensity for aggregation under certain conditions. Aggregates formed from wild-type acylphosphatase in the presence of 2,2,2-trifluoroethanol and from highly destabilized mutants are essentially identical in structure. Furthermore, it has been shown by mutational studies that different regions of the protein are important for aggregation and folding. In the present molecular dynamics study, we compare the behavior of the protein in aqueous solution and in a 25% (v/v) 2,2,2-trifluoroethanol/water environment mimicking the experimental conditions. The 2,2,2-trifluoroethanol surrounding affects the structure of the protein mostly in the regions important for aggregation, in good agreement with experimental data. This suggests that the early step of (partly) unfolding, which precedes the aggregation process, has been observed.
Flöck
Dagmar
D
Department of Chemistry, University of Rome La Sapienza, P.le Aldo Moro 5, Rome 00185, Italy.
Daidone
Isabella
I
Di Nola
Alfredo
A
D017766:Acid Anhydride Hydrolases / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D018397:Equidae; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009038:Motion; D019906:Nuclear Magnetic Resonance, Biomolecular; D017354:Point Mutation; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012997:Solvents; D014270:Trifluoroethanol / Q000494:pharmacology*; D014867:Water / Q000737:chemistry*; D000097024:Acylphosphatase
D017766:Acid Anhydride Hydrolases; D012997:Solvents; D014270:Trifluoroethanol; D014867:Water; D000097024:Acylphosphatase