# Artificial Photosynthesis: Is Computation Ready for the Challenge Ahead?
## 4 Protein/Surface Interactions
### Protein-(Self-Assembly Monolayer (SAM))-Metal Interface
Mcyt have the unique capability of long-range ET, even up to several micrometers [182], which can be applied for redox catalytic activities and electron storage [180; 183]. Conversely to one heme group cyt which are widely study, the absorption on a surface and its relative ET of Mcyt is still not well understood. Mcyt can form a network of ET pathways which facilitate the total ET, and can have potential applications in i.e., solar-conversion and bioenergy [182; 184]. [PERSON] et al. [185] studied a decaheme cyt folded in four domains adsorbed on a gold substrate via thiol bonding interactions (Figure 13). The aim of their  
Figure 12: Simulation-predicted electron-transfer pathway of cyt on negatively charged surfaces. Reprinted with permission from [179]. Copyright (2004) American Chemical Society. work was to assess which orientation and conformation of the adsorbed protein on gold will favor an efficient ET. Due to the complexity of the system studied, the authors devised a multiscale computational protocol in which full atomistic MD coupled with the molecular mechanics/Poison Boltzmann surface area (MM-PBSA) method are used to predict the configurations of the adsorbed protein on Au (111) surface. MM-PBSA has been shown to yield accurate prediction of the binding free energy of protein-surface interactions [186] and provides quantitative information on the driving and barrier forces of protein adsorption and docking. In the next step of their protocol, the authors perform Kinetic Monte Carlo (KMC) simulations [187] to study the ET across the protein and the hopping of electrons among the Fe atoms of the heme groups and their transfer to the surface. ET rate was quantified by using the nonadiabatic rate equation from the [PERSON] theory and the total ET flow assessed (Figure 13) [188]. As a result of this protocol, the authors were able to predict the Mcyt adsorption and ET rate when interacting with a flat gold surface. They demonstrated that the orientation of the protein, which in turn controls the ET flow, is controlled by the dehydration of the surface. Moreover, they found that this flow is more effective when the electrons move towards the interface, while is smaller in the reverse direction. Another widely used PPC in computational studied is azurin, yet only few studies reported a computational protocol when adsorbed on a metallic surface [189; 171]. Once again, MD is the method of choice to assess the conformation and orientation of the protein on the surface, as well as the retention of its folding upon adsorption. [PERSON] et al. [190] performed the study on an azurin (and several single amino acid mutations) adsorbed on gold surface without specific interaction, by mean of long MD simulations (up to 0.5 us) to describe the structural changes and dynamic of azurin adsorption. The authors found that the presence of a single amino acid mutation quenches the flexibility of some region of the protein, making it stiffer. This increase in stiffness affects the adsorption dynamics on gold; the wild type adsorbs with two preferential configurations (lying-down and anchored via  
Figure 13: (a,c) Phase diagram of the time-averaged electron occupation density \(\langle\)n\(\rangle\) for all 10 hemes in adsorbed structure as a function of the incoming (\(\alpha\)) and outgoing (\(\beta\)) electron transfer (ET) rates for the transfer direction heme10-to-heme5 (from the environment to the surface through the protein) and heme5-to-heme10 (from the surface to the environment through the protein), respectively. (b,d) The corresponding phase diagrams of the net electron flux J of adsorbed protein for the transfer direction heme10-to-heme5 and heme5-to-heme10, respectively. Reprinted with permission from [185]. Copyright (2016) American Chemical Society. hydrophobic parch) thanks to the higher mobility which allows for a reorientation of the structure during the adsorption process.