Electron transfer region of the CcP/Cytc complex.

<p>The ET pathway proposed by Pelletier and Kraut is shown in red, the ET pathway suggested by Siddarth is shown in blue.</p

Average distances <i>d</i> in Å, Electronic coupling <i>rmsV</i> in eV, Δ<i>G</i>° in eV, λ in eV and in s⁻¹ calculated for HT between donor and acceptor (DA), donor and bridge (DB), and bridge and acceptor (BA), respectively.

<p>The electronic coupling is calculated applying QM setups <i>direct</i>, <i>full</i>, <i>path1</i> and <i>path2</i>. <i>k_ET</i> is calculated by Marcus theory applying the respective highest electronic coupling of the system. Fluctuations are depicted through the coherence factor given in parentheses.</p

In-silico Assessment of Protein-Protein Electron Transfer. A Case Study: Cytochrome c Peroxidase – Cytochrome c

<div><p>The fast development of software and hardware is notably helping in closing the gap between macroscopic and microscopic data. Using a novel theoretical strategy combining molecular dynamics simulations, conformational clustering, <i>ab-initio</i> quantum mechanics and electronic coupling calculations, we show how computational methodologies are mature enough to provide accurate atomistic details into the mechanism of electron transfer (ET) processes in complex protein systems, known to be a significant challenge. We performed a quantitative study of the ET between Cytochrome c Peroxidase and its redox partner Cytochrome c. Our results confirm the ET mechanism as hole transfer (HT) through residues Ala194, Ala193, Gly192 and Trp191 of CcP. Furthermore, our findings indicate the fine evolution of the enzyme to approach an elevated turnover rate of 5.47×10⁶ s⁻¹ for the ET between Cytc and CcP through establishment of a localized bridge state in Trp191.</p> </div

Illustration of the key dihedral angle C16-C17-C18-H18 that determines the conversion of I1 to I2: a) A-I1; b) B-I1.

<p>Illustration of the key dihedral angle C16-C17-C18-H18 that determines the conversion of I1 to I2: a) A-I1; b) B-I1.</p

Docking score (MM/GBSA) of 9 carbocationic intermediates for 22 triterpenoid synthase homology models that follow channel C.

<p>Compounds that could not be successfully docked at all are arbitrarily assigned a docking score of −10 kcal/mol. Figure legend shows the UniProtKB IDs for the triterpenoid synthases. Panel a shows the docking scores against 8 lanosterol synthases (in red); panel b shows the docking scores against 10 cycloartenol synthases (in lime green); and panel c shows the docking scores against a cucurbitadienol synthase (in cyan), a parkeol synthase (in magenta) and 2 protostadienol synthases (in blue). Details c.f. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003874#pcbi.1003874.s006" target="_blank">Table S2</a>.</p

Intermediates and products of Channel C.

<p>Intermediates and products of Channel C.</p

A hypothetical example output of the carbocation docking.

<p>A hypothetical example output of the carbocation docking.</p

Example reactions of TPSs: a) limonene synthase; b) squalene-hopene cyclase.

<p>Example reactions of TPSs: a) limonene synthase; b) squalene-hopene cyclase.</p

Active site side chains minimized during the induced fit docking.^a

a<p>These residues were within 5 Å of the co-crystalized product lanosterol of 1W6K after superposition of 1SQC and 1W6K. The “flexible” side chains when docking against homology models are those aligned to the flexible residues of the corresponding templates.</p><p>Active site side chains minimized during the induced fit docking.^{<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003874#nt108" target="_blank">a</a>}</p

Example of constraints and restraints used during docking (residue numbering is for 1W6K).

<p>Example of constraints and restraints used during docking (residue numbering is for 1W6K).</p