Protein nanopores have been widely used as single-molecule sensors for the detection and characterization of biological polymers such as DNA, RNA, and polypeptides. A variety of protein nanopores with various geometries have been exploited for this purpose, which usually exhibit distinct sensing capabilities, but the underlying molecular mechanism remains elusive. Here, we systematically characterize the molecular transport properties of four widely studied protein nanopores, α-hemolysin, MspA, CsgG, and aerolysin, by extensive molecular dynamics simulations. It is found that a sudden drop in electrostatic potentials occurs at the sole constriction in MspA and CsgG nanopores in contrast to the gradual potential change inside α-hemolysin and aerolysin pores, indicating the crucial role of pore geometry in ionic and molecular transport. We further demonstrate that these protein nanopores exhibit open-pore currents and ssDNA-induced current blockades both in the order MspA > α-hemolysin > CsgG > aerolysin, but an equivalent blockade percentage around 80%. In addition, the substitution of key amino acids at the pore constriction, especially by charged ones, provides an efficient way to modulate the pore electrostatic potential and ionic current. This work sheds new light on the search for high-performance nanopores, engineering of protein nanopores, and design of bioinspired solid-state nanopores.