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.

Ranaudo, A., Cosentino, U., Greco, C., Moro, G., Bonardi, A., Maiocchi, A., et al. (2022). Evaluation of docking procedures reliability in affitins-partners interactions. FRONTIERS IN CHEMISTRY, 10 [10.3389/fchem.2022.1074249].

Evaluation of docking procedures reliability in affitins-partners interactions

Ranaudo, A
;
Cosentino, U;Greco, C;Moro, G;Bonardi A;
2022

Abstract

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.
Articolo in rivista - Articolo scientifico
affitins; antibody mimetics; consensus approach; diagnostic probes; DockQ; matrix of local coupling energies; molecular docking; protein-protein interaction;
English
Ranaudo, A., Cosentino, U., Greco, C., Moro, G., Bonardi, A., Maiocchi, A., et al. (2022). Evaluation of docking procedures reliability in affitins-partners interactions. FRONTIERS IN CHEMISTRY, 10 [10.3389/fchem.2022.1074249].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/397669
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