Transmembrane beta-barrels (TMBBs) belong to a special structural class of proteins predominately found in the outer membranes of Gram-negative bacteria, mitochondria and chloroplasts. TMBBs are surface-exposed proteins that perform a variety of functions ranging from nutrient acquisition to osmotic regulation. These properties suggest that TMBBs have great potential for use in vaccine or drug therapy development. However, membrane proteins, such as TMBBs, are notoriously difficult to identify and characterize using traditional experimental approaches and current prediction methods are still unreliable.