Tight junction (TJ) protein assembly controls permeability across epithelial and endothelial cells; thus, biochemical interactions that control the TJ assembly have physiological and biomedical significance. In this work, we employed multiscale simulations to probe the TJ self-assembly of five classic claudins (-1, -2, -4, -15, and -19). Claudin proteins assembled into dimeric and occasionally trimeric interfaces that subsequently formed larger polymeric strands. Using orientation-angle analysis to decompose polymeric strands, we found that individual claudins prefer certain dimer interfaces to others. Despite variations in the exact dimer populations observed in individual claudins, there appears to be an overall conformational uniformity in the type of dimeric interactions formed by the claudin family of proteins. A detailed structural characterization of the trimeric assemblies revealed that they could be putative receptors for trimeric Clostridium perfringens enterotoxin. Full characterization of the claudin-2 dimer interface revealed a cysteine cross-linkable interaction, which could be assembled into a symmetric pore of 7.4 Å average diameter. We extended the analysis of pore structure to other classic claudins and found that the distribution of polar residues lining the pore volume varied considerably between the barrier- and pore-forming claudins, potentially delineating the functionality in classic claudins.