Molecular machines (MM) are essential components of living cells. They conduct mechanical work, transport materials into and out of cells, assist in processing enzymatic reactions, and more. Their operations are frequently combined with significant conformational transitions. Computational studies of these conformational transitions and their coupling to molecular functions are discussed. It is argued that coarse descriptions of these molecules which are based on mass density and shape provide useful information on directions of action. It is further argued that MM are likely to have well focused and narrow reaction pathways. The proposal for such pathways is supported by evolutionary analyses of homologous machines. Finally, these observations are used to build atomically detailed models of these systems that are making the link from structure to functions (kinetics and thermodynamics). For that purpose enhanced sampling techniques are required. âº Elastic models of proteins capture large-scale motions of motors. âº Function of motors is embedded in native contacts and evolutionary patterns. âº Reaction path models motor motions by a tube of minimum free energy path. âº Milestoning correlates structure and function of atomic models of motors.