This data collection contains additional data related to Schnee et al.: Mechanistic basis of the increased methylation activity of the SETD2 protein lysine methyltransferase towards a designed super-substrate peptide. This includes MD simulations code and analysis scripts. The usage of these Phyton scripts is further explained in the enclosed readme file. In additon, the repository contains three supplementary movies provided at different resolution and source data underlying the plots shown in the figures of the accompanying manuscript as excel table.