Molecular Dynamics Simulations of Cytochrome c unfolding in AOT Reverse Micelles: the first steps

Stéphane Abel (1) , Marcel Waks (2) , Massimo Marchi (1)

1 SB2SM - Service de Bioénergétique, Biologie Stucturale, et Mécanismes
2 LIP - Laboratoire d'Imagerie Paramétrique

This paper explores the reduced form of horse cytochrome c confined in reverse micelles (RM) of sodium bis-(2-ethylhexyl) sulfosuccinate (AOT) in isooctane by molecular dynamics simulation. RMs of two sizes were constructed at a water content of Wo =[H2O]/[AOT] = 5.5 and 9.1. Our results show that the protein secondary structure and the heme conformation both depend on micellar hydration. At low hydration, the protein structure and the heme moiety remain stable, whereas at high water content the protein becomes unstable and starts to unfold. At Wo =9.1, according to the X-ray structure, confor- mational changes are mainly localized on protein loops and around the heme moiety, where we observe a partial opening of the heme crevice. These findings suggest that within our time window (10 ns), the struc- tural changes observed at the heme level are the first steps of the protein denaturation process, previously described experimentally in micellar solutions. In addition, a specific binding of AOT molecules to a few lysine residues of the protein was found only in the small-sized RM.

Mots clés: AOT; reverse micelle; horse cytochrome c; confined protein; protein stability; molecular dynamics simulation

Domaines: Chimie théorique et/ou physique; Biophysique [physics.bio-ph]; Biologie structurale [q-bio.BM]

Stéphane Abel, Marcel Waks, Massimo Marchi. Molecular Dynamics Simulations of Cytochrome c unfolding in AOT Reverse Micelles: the first steps. European Physical Journal E: Soft matter and biological physics, 2010, 32 (1), pp.399-409. ⟨10.1140/epje/i2010-10635-x⟩. ⟨hal-00436326⟩