Abstract: The analysis of protein 3D structure is an important step to understand their mechanism of action, regulation, function and family’s belonging. Experimental methods for proteins structure determination don’t keep up with the increasing number of genomic sequence available: this led to an increase of computational methods that predict three-dimensional model for a protein of unknown structure (target) on the basis of sequence similarity to proteins of known structure (templates). There are different kinds of Homology Modelling methods, but all of them can’t recover from an incorrect target-template alignment: a good alignment is the first think to be considered when we’re talking about model’s confidence. SWISS MODEL, an automated comparative protein modelling server starts with the analysis of the structural conserved regions in the target-templates alignment. Ras protein are highly conserved GTPase playing a pivotal role in different important cellular events: cell proliferation, differentiation, cellular traffic and cytoskeleton organization. Within cells, Ras proteins exist both in a GTP-bound form (“on” state) or a GDP-bound (“off” state). The level of the GTP-bound state derives from the balance of the activity of the GTPase Activating Proteins (GAPs) and Guanine nucleotide Exchange Factors (GEFs). Common feature of all Ras GEFs is the presence of a domain, the RasGEF domain, carrying all the main structural features needed to interact with Ras and to exchange the nucleotide. A notable feature of this catalytic domain is the protrusion of a hairpin, formed by helices αH and αI, out of the core of the domain. It has been proposed helix αH plays an important role in the nucleotide-exchange mechanism opening up the nucleotide-binding site.