We have studied large-scale conformational transitions in the maltose-binding protein, and the nucleotide binding domains of a maltose-transporter using enhanced conformational sampling in Cartesian collective variables (CVs) with temperature-accelerated molecular dynamics (TAMD), and C(α)-based elastic network normal mode analysis. Significantly, every functional displacement in the TAMD-generated pathways of each protein could be rationalized via a single low-frequency soft mode, while a combination of 2 to 3 low-frequency modes were found to describe the entire conformational change suggesting that collective functional movement in TAMD trajectories is facilitated by the intrinsically accessible low-frequency normal modes. By applying a harmonic potential to facilitate functional motion in TAMD simulations, we also provide a recipe to reproducibly generate structural transitions in both proteins, which can be used to characterize large-scale conformational changes in other biomolecules.