The pi-stacking between aromatic oligomers has been extensively studied for many years, although the notion of exploiting this phenomenon as the driving force for molecular actuation has only recently emerged. In this work we examine with MP2 and Car-Parrinello ab initio calculations the actuation properties of a novel class of thiophene-based materials introduced by Swager et al. (Adv. Mater. 2002, 14, 368; J. Am. Chem. Soc. 2003, 125, 1142). The chemical ingredients of the assembly, calix[4]arenes and oligothiophenes, are screened separately to characterize the actuation mechanisms and design optimal architectures. In particular, ab initio methods are used to study pi-stacking in mixed-valence oligothiophene dimers, revealing strong interactions that can be turned on and off as a function of the electrochemical potential. We show how these interactions could be harnessed to achieve molecular actuation and investigate the response of an active unit in real time with first-principles molecular dynamics simulations.