Beta Barrel Membrane Proteins: 3-D Long Loop Modelling and Computational Stability Analysis

Beta-barrel membrane proteins are found in the outer membrane of gram-negative bacteria, mitochondria, and chloroplasts. This work examines both the structure of the loop region and investigates the transmembrane region. In the first part of this work, we model long loop in LptD beta barrel membrane protein, which can facilitate studies the extracellular loop regions of the protein LptD, an essential OMP that inserts lipopolysaccharide endotoxins into the outer membrane of Escherichia coli. LptD contains 26 strands and 13 loops. Currently, accurate models have been predicted for short loops with <18 residues. With pretzel, we aim to model one of the loops of LptD that is 35 residues long. In the second part of the work, we explore a computational strategy to stabilize beta barrel transmembrane proteins using eukaryotic mitochondrial protein, OmpG as our system. We design a set of novel βMPs structure based on OmpG. We evaluate designs of new beta barrel membrane protein structures for wild-type OmpG that contain 14 strands and 7 loops, where a new beta hairpin is inserted at various places in the wild-type OmpG for 7 experimentally generated sequences. Using improved energy function, we predict the best possible beta barrel stable structure.