Molecular transport properties in short cylindrical and pyramidal nanopores are investigated by mesoscale dissipative particle dynamics simulations. We examine the effect of pore geometry, size, flow direction, particle diameter and electrostatic forces on membrane flux, selectivity and fouling. Biomolecules of various sizes are represented by spherical particles as they move through nanopores. The highest molecular concentration in pores is obtained with a cylindrical geometry, whereas the lowest concentration is obtained with a pyramidal geometry when the molecular transport direction is from large to small pore opening. This reveals a higher tendency for fouling in cylindrical pores relative to pyramidal pores. In general, increasing pore size and decreasing molecular diameter increase diffusion and fluxes, as expected, and the highest fluxes are achieved when the molecule is in neutral state. For large, short pores, higher diffusion rates are achieved with a cylindrical geometry compared to a pyramidal geometry. For pore: particle diameter ratios below 10, highly restricted motion is observed. In the presence of electrostatic forces, the molecular separation potential of pyramidal pores is 1.5× higher relative to short cylindrical pores, although the diffusion rate with cylindrical pores is 1.8× higher. Finally, we demonstrate that decreasing the pore size by a factor of 1.2 can reduce the pore molecular concentration by at least a factor of 3 for all pore types. This finding is consistent with a surprising recent experimental study in which larger ceramic pores were observed to foul much faster than smaller pores. This journal is © 2012 the Owner Societies.