Abstract: The information carried by the aminoacidic sequence can be used by different bioinformatic methods, in order to predict the 3D structure of a protein or its domains. The tools for sequence alignment permit to individuate homologous regions among proteins, and this represent the basis for a homology modeling procedure. The algorithms of secondary structure prediction use chemical, physical and statistical parameters to recognize if a region of sequence could assume a specific secondary structure. Fold recognition servers can test if a protein sequence is compatible with one of the known folds in the PDB. If these different tools give rise to homogeneous responses, it is possible to predict with good reliability the fold of a protein or single domains of unknown structure. hSos1 is a multidomain protein involved in the activation of the Ras signaling by catalyzing guanine nucleotide exchange on Ras. The Ras-GEF domain of hSos1 (Sos-Cat) is flanked by amino- and carboxyl-terminal regions, which are able to inhibit hSos1 activity towards Ras. To investigate the structural determinants of this inhibition, it is necessary to know the structural features of the involved domains. The carboxyl terminus of hSos1 contains a proline rich domain with consensus sequences for binding to the SH3 domains, while the amino-terminal region of hSos1 includes three domains: Histone domain, Dbl Homology domain (DH) and Pleckstrin homology domain (PH). The Histone domain is involved in the inhibition of the Ras-GEF activity of hSos1. It can also bind the PH domain, while it cannot interact with the DH domain. The DH domain is implicated in the inhibition of the Ras-GEF activity of hSos1, possibly through direct interaction with Sos-Cat. The PH domain is able to interact with the DH domain; the crystal structure of the PH-DH complex is available. We have focused on the intra-molecular interactions that occur among these domains in the activation/inhibition of hSos1 by means of computational tools, like the low-resolution protein-protein docking. The essence of the procedure is the reduction of protein structures to digitized images on a three-dimensional grid. The structural elements smaller than the step of the grid (e.g., atom-size) are not present in the docking. This feature permits to reduce the negative effect of structural changes upon complex formation on docking calculation.