Bio-metal organic frameworks (Bio-MOFs), composed of biocompatible metal cations and linker molecules such as amino acids, nucleobases and sugars, are considered as promising candidates for gas storage and separation due to their permanent porosity, chemical functionality and structural tunability. In this study, detailed molecular simulations were performed to assess the potential of 10 different bio-MOFs in adsorption-based and membrane-based separation of CO2/CH4 mixtures. After showing the good agreement between experiments and molecular simulations for single-component adsorption isotherms of several gases in various bio-MOFs, adsorption selectivity and working capacity of these materials were predicted for CO2/CH4 separation. Membrane selectivity and gas permeability of bio-MOFs were computed considering flexibility of the structures in molecular simulations for the first time in the literature. Results showed that several bio-MOFs outperform widely studied MOFs and zeolites both in adsorption-based and membrane-based CO2/CH4 separations. Bio-MOE-1, bio-MOF-11 and bio-MOF-12 were identified as promising adsorbents and membranes for natural gas purification. (C) 2015 Elsevier Ltd. All rights reserved.