Molecular Dynamics Simulations of the Elusive Matrix‐Open State of Mitochondrial ADP/ATP Carrier

Abstract

AbstractWe studied and compared in detail an elusive matrix open (m‐state) and cytoplasmic open (c‐state) state of ADP/ATP carrier (AAC) protein embedded in the DOPC bilayer by microsecond molecular dynamics (MD) simulations. We analyzed both states with and without cardiolipin (CDL) molecules, with a special emphasis on the recently obtained crystallographic structure of the AAC m‐state. The obtained results show that both states of the protein are stable in the DOPC bilayer and impermeable to water. In comparison with the c‐state of AAC, the m‐state is more dynamic, but at the same time possesses a larger occluded area in the protein cavity. Both states of the protein are less flexible in simulations when CDL molecules are present, which is especially visible for the m‐state. Finally, the analysis of the protein conformational changes during MD simulations shows that protein parts at the protein/lipid boundaries are prone to larger conformational changes in contrast to central region of the protein embedded in the bilayer core, thus further supporting the cycling mechanism suggested for ADP/ATP exchange by AAC.