Molecular Basis of Coupled Protein and Electron Transfer Dynamics of Cytochrome c in Biomimetic Complexes

Abstract

Direct electron transfer (ET) of redox proteins immobilized on biomimetic or biocompatible electrodes represents an active field of fundamental and applied research. In this context, several groups have reported for a variety of proteins unexpected distance dependencies of the ET rate, whose origin remains largely speculative and controversial, but appears to be a quite general phenomenon. Here we have employed molecular dynamics (MD) simulations and electron pathway analyses to study the ET properties of cytochrome c (Cyt) electrostatically immobilized on Au coated by carboxyl-terminated alkylthiols. The MD simulations and concomitant binding energy calculations allow identification of preferred binding configurations of the oxidized and reduced Cyt which are established via different lysine residues and, thus, correspond to different orientations and dipole moments. Calculations of the electronic coupling matrices for the various Cyt/self-assembled monolayer (SAM) complexes indicate that the thermodynamically preferred protein orientations do not coincide with the orientations of optimum coupling. These findings demonstrate that the ET of the immobilized Cyt is controlled by an interplay between protein dynamics and tunneling probabilities. Protein dynamics exerts two level of tuning on the electronic coupling via reorientation (coarse) and low amplitude thermal fluctuations (fine). Upon operating the Au support as an electrode, electric-field-dependent alignment of the protein dipole moment becomes an additional determinant for the protein dynamics and thus for the overall ET rate. The present results provide a consistent molecular description of previous (spectro)electrochemical data and allow conclusions concerning the coupling of protein dynamics and ET of Cyt in physiological complexes.

Alternative ground states enable pathway switching in biological electron transfer

“…In fact, the study of the Cyt 552 -Cu A complex reveals subtle structural perturbations at the Cu A site in a redox state-dependent fashion (13). In addition, the prediction that moderate electric fields alter the barrier for σ u *-π u interchange suggests that the local membrane potential could exert regulation on the electroprotonic energy transduction, as previously proposed based on different evidence (31,32). Of utmost importance, however, even in the absence of external perturbations, the enhanced superexchange coupling of the π u state renders it suitable for participating in the ET reaction, even if poorly populated.…”

Kinetics, subcellular localization, and contribution to parasite virulence of a Trypanosoma cruzi hybrid type A heme peroxidase ( Tc APx-CcP)

“…The probability of ET toward the ferryl-oxoheme group was calculated using the pathways algorithm (56,57). This method looks for the best possible path connecting the electron donor and the acceptor, and it was successfully used by our group previously (58)(59)(60)(61)(62). Briefly, according to the Marcus theory (63), the ET rate constant (k ET ) depends on the reaction standard free energy (ΔG°), the reorganization energy (λ), and the electronic coupling matrix (T DA ), described in the following equation:…”

Modeling and simulation of protein–surface interactions: achievements and challenges

“…The properties of SAMs have been reviewed in (Chaki & Vijayamohanan, 2002;Gooding et al 2003;Love et al 2005;Senaratne et al 2005). Modeling of protein-SAM interactions has been reported, mostly for alkanethiol SAMs, in (Alvarez-Paggi et al 2010;Hsu et al 2008;O'Mahony et al 2013;Sun et al 2005;Utesch et al 2013;Wang et al 2010a, b;Xie et al 2012) and peptide-SAM interactions have been modeled by Nowinski et al (2012).…”

“…Examples include simulations for structural refinement of docked complexes (Aliaga et al 2011;Alvarez-Paggi et al 2013;Brancolini et al 2012Brancolini et al , 2015Imamura et al 2007), and for the investigation of the binding orientations of proteins on surfaces (Alvarez-Paggi et al 2010;Boughton et al 2010;Coppage et al 2013); the kinetic mechanisms of adsorption (Raffaini & Ganazzoli, 2010); the ET pathways and properties of adsorbed proteins (Bizzarri, 2006;Siwko & Corni, 2013;Utesch et al 2012;Zanetti-Polzi et al 2014;Zhou et al 2004); the effects of pH (Emami et al 2014b;Imamura et al 2003;Tosaka et al 2010;Utesch et al 2013) and ionic strength (Bizzarri, 2006) on adsorption; the role of ions in mediating adsorption ; and structural and energetic aspects of adsorption of proteins on surfaces (Apicella et al 2013;Jose & Sengupta, 2013;Hoefling et al 2011;Hung et al 2011;Kubiak-Ossowska & Mulheran, 2010a, b;O'Mahony et al 2013;Vila Verde et al 2009Wang et al 2010a, b;Yu et al 2012a;Steckbeck et al 2014;Sun et al 2014a;Sun et al 2014b). Further, conventional MD can be used to simulate physical perturbations, such as mechanical or electrical forces exerted on molecules in experiments.…”