Here we present a detailed workflow for clustering and enhanced sampling of biomolecular conformations using the ShapeGMM methodology. This approach fits a probabilistic model of biomolecular conformations rooted in the idea that the free energy can expressed in terms of local fluctuations in atomic positions around metastable states. We demonstrate using a single model system how to generate and fit equilibrium molecular dynamics simulation data. We then show how to use the resulting model to generate a reaction coordinate between two states, how to sample along that coordinate using Metadynamics using our size-and-shape PLUMED module, and how to cluster those biased conformations to give a refined equilibrium ShapeGMM model.