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Integrin conformational dynamics are critical to their receptor and signaling functions in many cellular processes, including spreading, adhesion, and migration. However, assessing integrin conformations is both experimentally and computationally challenging because of limitations in resolution and dynamic sampling. Thus, structural changes that underlie transitions between conformations are largely unknown. Here, focusing on integrin αvβ(3), we developed a modified form of the coarse-grained heterogeneous elastic network model (hENM), which allows sampling conformations at the onset of activation by formally separating local fluctuations from global motions. Both local fluctuations and global motions are extracted from all-atom molecular dynamics simulations of the full-length αvβ(3) bent integrin conformer, but whereas the former are incorporated in the hENM as effective harmonic interactions between groups of residues, the latter emerge by systematically identifying and treating weak interactions between long-distance domains with flexible and anharmonic connections. The new hENM model allows integrins and single-point mutant integrins to explore various conformational states, including the initiation of separation between α- and β-subunit cytoplasmic regions, headpiece extension, and legs opening.