J. Phys. Chem. B, 108 (41), 16250 -16254, 2004. 10.1021/jp048788l S1089-5647(04)08788-7
Web Release Date: September 17, 2004
Copyright (c) 2004 American Chemical Society

A molecular dynamics study of acylphosphatase in aggregation-promoting conditions: The influence of trifluoroethanol/water solvent

Dagmar Floeck, Isabella Daidone, Alfredo Di Nola *
Department of Chemistry, University of Rome La Sapienza, P.le Aldo Moro 5, Rome 00185, Italy
email: Alfredo Di Nola (dinola@degas.chem.uniroma1.it)

*Correspondence to Alfredo Di Nola, Department of Chemistry, University of Rome La Sapienza, P.le Aldo Moro 5, Rome 00185, Italy
Funded by:
European Community Training and Mobility Research Network Project Protein (Mis)folding; Grant Number: HPRN-CT-2002-00241

Keywords: protein aggregation . protein misfolding . essential dynamics

FULL TEXT

Abstract

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. (c) 2004 Wiley Periodicals, Inc. Biopolymers, 2004