Understanding protein folding and function is one of the most important problems in biological research. Energy landscape theory and the folding funnel concept have provided a framework to investigate the mechanisms associated to these processes. Since protein energy landscapes are in most cases minimally frustrated, structure based models (SMBs) have successfully determined the geometrical features associated with folding and functional transitions. However, structural information is limited, particularly with respect to different functional configurations. This is a major limitation for SBMs. Alternatively, statistical methods to study amino acid co-evolution provide information on residue-residue interactions useful for the study of structure and function. Here, we show how the combination of these two methods gives rise to a novel way to investigate the mechanisms associated with folding and function. We use this methodology to explore the mechanistic aspects of protein translocation in the integral membrane protease FtsH. Dual basin-SBM simulations using the open and closed state of this hexameric motor reveals a functionally important paddling motion in the catalytic cycle. We also find that Direct Coupling Analysis (DCA) predicts physical contacts between AAA and peptidase domains of the motor, which are crucial for the open to close transition. Our combined method, which uses structural information from the open state experimental structure and co-evolutionary couplings, suggests that this methodology can be used to explore the functional landscape of complex biological macromolecules previously inaccessible to methods dependent on experimental structural information. This efficient way to sample the conformational space of large systems creates a theoretical/computational framework capable of better characterizing the functional landscape in large biomolecular assemblies.