Improved membrane protein topology prediction by domain assignments

Topology predictions for integral membrane proteins can be substantially improved if parts of the protein can be constrained to a given in/out location relative to the membrane using experimental data or other information. Here, we have identified a set of 367 domains in the SMART database that, when found in soluble proteins, have compartment‐specific localization of a kind relevant for membrane protein topology prediction. Using these domains as prediction constraints, we are able to provide high‐quality topology models for 11% of the membrane proteins extracted from 38 eukaryotic genomes. Two‐thirds of these proteins are single spanning, a group of proteins for which current topology prediction methods perform particularly poorly.