The present invention relates to a computer-implemented method of predicting site-specific mutation activity of an antigen, said method comprising (a) providing in silico at least one three-dimensional structure of said antigen, preferably an ensemble of three-dimensional structures of said antigen; (b) providing in silico at least one three-dimensional structure of at least one antibody or fragment thereof capable of binding to or specific for said antigen, preferably an ensemble of three-dimensional structures of said antibody or fragment thereof; (c) determining in silico the accessibility of the structure(s) of (a) to the structure(s) of (b), wherein higher accessibility is indicative of higher mutation activity, in particular under selective pressure exerted by said antibody or fragment thereof; thereby predicting said site-specific mutation activity.