Improving 3D Structure Prediction of Beta-Barrel Membrane Proteins

Abstract

Beta-barrel membrane proteins are found in the outer membrane of gram-negative bacteria, mitochondria, and chloroplasts. They carry out diverse biological functions, including pore formation, membrane anchoring, enzyme activity, and bacterial virulence. In addition, beta-barrel membrane proteins increasingly serve as scaffolds for bacterial surface display and nanopore-based DNA sequencing. Due to difficulties in experimental structure determination, they are sparsely represented in the protein structure databank and computational methods are required to understand their biophysical principles. We have developed a novel 3D structural template for the construction of beta-barrel membrane proteins, which captures major geometric properties of these proteins. With the help of the prediction procedure of strand registers that we developed, we have achieved a high accuracy for the structure prediction of beta-barrel proteins. In addition, for the beta-barrel proteins with irregular barrel shape, we have further developed an elastic model, which characterizes bending and curvatures of the barrels, to improve the structure prediction of these proteins.