# Artificial Photosynthesis: Is Computation Ready for the Challenge Ahead?
## 4 Protein/Surface Interactions
### Protein-(Self-Assembly Monolayer (SAM))-Metal Interface  
MD is the method of choice when conformational studies are considered. Generally, these models consist of an idealized structure of the solid surface, which might not be representative of the actual experimental system, and simplifications on both the bond-topological structure and protein structure, protonation and interfacial solvent structure often affect the setting up of the MD simulations. Noble metals such as silver and gold are the most common metals used in experimental applications, like biosensors and bio-electronic electrodes [175; 176]. The substrate is commonly considered crystalline, while in experiments often amorphous or polycrystalline surfaces are present. This latter case is especially interesting, since changing the adsorption facet of i.e., Au for a protein, can lead to strongly facet-dependent results [177]. In fact, for flat, planar Au surface, the facet of choice is the Au (111), as it is assumed to be the dominant one. While this is true for planar interfaces, more care must be payed when nanoparticles are considered, since there is still debates on which facet is the predominant one. Moreover, the presence of structural defects on the surface, as well as the presence of various functionalizations might have a strong impact on the protein conformations, and shall not be neglected when such analyses are planned from a computational side. In addition, often self-assembly monolayer (SAM) are present in between the metal and the protein. SAM are thin films of molecules which spontaneously adsorbed in an ordered assembly over the metal (often Au). Typically, SAM are chemisorbed on the substrate through their reactive anchoring group (i.e., thiol or silate) to form a very stable assembly, and present a tail group which can be functionalized by small organic groups or even proteins. Together with the length of the SAM forming molecule itself, these characteristics determine a change in the physico-chemical properties of the metal surface and can be adjusted accordingly to the desired application. Moreover, the presence of a SAM allows for specific absorption interaction with the protein, limiting and sometime imposing a specific orientation of the biological component on the SAM, which, in turn determine the ET ability of the interface. Finally, SAMs act as electrical insulators, passivating the metal surface [178], protecting if from degradation (i.e., in case of metal oxides). One well known system often use in computation is cytochrome \(c\) (cyt). Cyt plays an important role in a variety of artificial bio-applications like biosensors, bioelectronic devices and biofuel cells, and its adsorption on a SAM covered gold surface has been extensively studied. For these applications, the knowledge and ability of orienting the cyt on the SAM is crucial, as on it depends the ET ability of the whole interface. It has been reported that to obtain a fast ET, the protein should be oriented with the heme ring close to the SAM, in a perpendicular orientation [179] (Figure 12). By mean of combined Monte Carlo and MD simulations, the authors of this work assessed the conformation and orientation of cyt adsorbed on a negatively charged carboxyl-terminated SAM-Au surface. Cyt could orient itself with the heme group perpendicular to the surface, forcing a specific direction of the dipole moment which is a key parameter on the determination of the final orientation. On the basis of these results, the authors indicate a possible ET pathway, from the iron of heme to the surface through a series of specific amino acids. Moreover, they warm the readers on the effect of a charged surface, which can be detrimental for the function of the protein itself. Beside cytochrome, multheme cytochrome (Mcyt) are a family of proteins in which two or more heme center are present, with Fe-Fe distance shorter than 1.55 nm [180; 181].