Ž . Biophysical Chemistry 81 1999 197]205 Molecular dynamics simulations of Cu,Zn superoxide dismutase: effect of temperature on dimer asymmetry M. Falconi a , S. Melchionna b , A. Desideri a,U a INFM and Department of Biology, Uni¤ ersity of Rome ‘Tor Vergata’, Via della Ricerca Scientifica, 00133 Rome, Italy b Department of Chemistry, Uni¤ ersity of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK Received 10 May 1999; received in revised form 21 July 1999; accepted 21 July 1999 Abstract Molecular dynamics simulations of solvated dimeric Cu,Zn superoxide dismutase have been carried out at four temperatures, namely 200, 225, 250 and 300 K. Analysis of the backbone-to-backbone hydrogen bonds number indicates that the symmetry observed in the two subunits at 200 K is gradually lost by heating the system. The C a atoms displacement cross-correlation maps confirm that the asymmetric behaviour of the two subunits increases as a function of temperature. The dynamic cross-correlation of the subunits volumes indicates a fast correlation between the two subunits at 300 K, which is delayed upon lowering the simulation temperature. These results indicate that temperature plays an essential role in injecting such an asymmetry; the two subunits being asymmetric and in rapid communication at 300 K, and almost symmetric and in slow communication at lower temperatures. Q 1999 Elsevier Science B.V. All rights reserved. Keywords: Molecular dynamics simulation; Cu,Zn superoxide dismutase; Structure ]function relationship; Transition temperature; Dynamical cross-correlation 1. Introduction Ž . Superoxide dismutases Cu,Zn SODs are a class of metallo-enzymes that catalyse the dismu- U Corresponding author. Tel.: q39-06-72594376; fax: q39- 06-72594326. Ž . E-mail address: desideri@uniroma2.it A. Desideri tation of superoxide into oxygen and hydrogen peroxide by alternate reduction and oxidation of a copper ion which constitutes the active redox wx site 1 . The functional properties of this enzyme has been extensively studied by a series of pro- jects based on site directed mutagenesis which have shown that the catalytic rate of the enzyme is diffusion limited and that the fully conserved Arg 141 plays an essential role in both the attrac- 0301-4622r99r$ - see front matter Q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S 0 3 0 1 - 4 6 2 2 99 00094-0