• The idea of combining the CREST conformational search workflow with the subsequent DFTB3+MBD geometry optimization, both in gas phase and implicit water, has provided us with access to a more extensive and reliable exploration of low-and high-energy (compact/extended) conformers of large molecules. To the best of our knowledge, this procedure has not been considered in previous works. Also, notice that MBD interaction is a key factor in accurately describing and identifying diverse conformations in large molecular complexes, due to their anisotropic shapes.