We investigate the conformational ensembles of macrocyclic compounds and the influence of solvent polarity and noncovalent interactions on the composition of solution ensembles with the long term goal to provide an improved understanding of macrocycles membrane permeability and bioactivity. We are part of the European Doctoral network 'Macrocycles for Drug Discovery' (MC4DD) and have just employed 3 additional PhD students on this project, which increased our need for computational resources. The project is supported by this EU DN grant the coming 5 years. Some of our previous results on this project ware summarized in the papers J. Med. Chem. 2025, 68, 368; Chem. Eur. J. 2024, e202401654; Drug Discovery Today 2024, 103917; Nature Rev. Chem. 2024, 8, 45; Nature Rev. Chem. 2023, 7, 511; Eur J. Org. Chem. 2023, e202201280​; Chem. Eur. J. 2022, e202202798​; ACS Med. Chem. Lett. 2021, 12, 983-990; Chem. Eur. J. 2020, 26, 5231-5244; ACS Omega, 2019, 4, 22245; J. Med. Chem. 2019, 62, 111071; Chem. Eur. J. 2019, 25, 14572-14582; ACS Omega 2018, 3, 11742; ACS Omega 2017, 2, 508). In this project we use Monte Carlo conformational search as an input for a combined computational and spectroscopic ensemble analysis (NAMFIS). Some MD and DFT work will also be done. We have been regular users at NSC and HP2CN over the past years, have all the software we need running, and a good routine with running calculations. We wish to primarily use Schrödinger Maestro on NSC (tetralith).