Over the past two decades, Ion Mobility-Mass Spectrometry (IM-MS) 132 has greatly advanced as an important method in metabolomics applications for the characterization of small molecules in the gas-phase. The technique of ion mobility spectrometry (IMS) measures an ions drift time through a gas-filled region (N2 or He) under the influence of an electric field, efficiently separating gas-phase molecular ions based on charge, size, and shape. IM-MS integrates diverse technologies like traveling wave (TWIMS) , drift tube (DTIM) , trapped IM (TIMS) , and differential mobility MS (DMS) , in combination with ionization methods such as matrix-assisted laser desorption ionization (MALDI), electrospray ionization (ESI), and atmospheric pressure chemical ionization (APCI). It seamlessly accommodates liquid-phase separations including capillary electrophoresis, gas chromatography, and supercritical fluid chromatography. Unlike traditional techniques like X-ray crystallography and NMR spectroscopy, IM-MS is rapid, bypassing the need for prior purification or crystallization of the target compound. The technique doesn't directly measure molecular surfaces, instead, it derives collision cross-section (CCS) values from mobility data using a mathematical model. These CCS values are key for understanding the conformational features of molecules and enable comparison with experimental values for accurate and consistent results. The term Collision Cross Section was historically associated with the hard sphere collision model. Theoretically, CCS is computed by averaging the cross-sectional area of rotation for a target molecular ion using the Mason-Schamp equation. This process relies on input atomic coordinate files derived from various sources, including X-ray scattering, NMR data, quantum chemical calculations, or molecular dynamics (MD) simulations. Three distinct computational treatments of ion-buffer gas collisions are in general use: projection approximation (PA) , exact hard sphere scattering (EHSS) 141 , and the trajectory method (TM) 141 are all employed in CCS estimation. To achieve accurate CCS predictions, it is essential to calculate all potential collision angles between a buffer gas and the target molecule. The precision of CCS prediction is contingent upon effectively sampling the correct conformational space. Consequently, the initial generation of the conformation ensemble plays a pivotal role in predicting accurate CCS values and, by extension, the correct three-dimensional structure in the gas phase.