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Affitins constitute a class of small proteins belonging to Sul7d family, which, in microorganisms such as Sulfolobus acidocaldarius , bind DNA preventing its denaturation. Thanks to their stability and small size (60-66 residues in length) they have been considered as ideal candidates for engineering and have been used for more than 10 years now, for different applications. The individuation of a mutant able to recognize a specific target does not imply the knowledge of the binding geometry between the two proteins. However, its identification is of undoubted importance but not always experimentally accessible. For this reason, computational approaches such as protein-protein docking can be helpful for an initial structural characterization of the complex. This method, which produces tens of putative binding geometries ordered according to a binding score, needs to be followed by a further reranking procedure for finding the most plausible one. In the present paper, we use the server ClusPro for generating docking models of affitins with different protein partners whose experimental structures are available in the Protein Data Bank. Then, we apply two protocols for reranking the docking models. The first one investigates their stability by means of Molecular Dynamics simulations; the second one, instead, compares the docking models with the interacting residues predicted by the Matrix of Local Coupling Energies method. Results show that the more efficient way to deal with the reranking problem is to consider the information given by the two protocols together, i.e. employing a consensus approach., Competing Interests: Author AM is employed by Bracco S.p.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ranaudo, Cosentino, Greco, Moro, Bonardi, Maiocchi and Moroni.)

Carbon monoxide (CO) is a highly toxic gas to many living organisms. However, some microorganisms are able to use this molecule as the sole source of carbon and energy. Soil bacteria such as the aerobic Oligotropha carboxidovorans are responsible for the annual removal of about 2 x 10 8 tons of CO from the atmosphere. Detoxification through oxidation of CO to CO 2 is enabled by the MoCu-dependent CO-dehydrogenase enzyme (MoCu-CODH) which-differently from other enzyme classes with similar function-retains its catalytic activity in the presence of atmospheric O 2 . In the last few years, targeted advancements have been described in the field of bioengineering and biomimetics, which is functional for future technological exploitation of the catalytic properties of MoCu-CODH and for the reproduction of its reactivity in synthetic complexes. Notably, a growing interest for the quantum chemical investigation of this enzyme has recently also emerged. This mini-review compiles the current knowledge of the MoCu-CODH catalytic cycle, with a specific focus on the outcomes of theoretical studies on this enzyme class. Rather controversial aspects from different theoretical studies will be highlighted, thus illustrating the challenges posed by this system as far as the application of density functional theory and hybrid quantum-classical methods are concerned.