Hence, in this work, we hypothesize that gas-phase IM-MS studies sample the gas-phase conformational ensemble of a molecule providing unique insights into the shape and, hence, the structure of a molecule in the gas- phase. Importantly, we are assuming the drift gas (usually N2 or He) has a minimal perturbation on the gas-phase molecular structure. Based on this hypothesis, we propose a novel approach to evaluate and compare gas-phase conformational search engines based on their ability to characterize the gas-phase conformational ensemble and identify the global minima using a quantum mechanics (QM) based workflow whose outcomes are compared against experimental IM-MS information. 9,10 Specifically, we have developed a QM-based method to calculate Collisional Cross Sections (CCS), which is an accurate indicator of the global minima for molecular structures in the gas-phase .