title: Optimal mutation sites for PRE data collection and membrane protein structure prediction.
abstract: Nuclear magnetic resonance paramagnetic relaxation enhancement (PRE) measures long-range distances to isotopically labeled residues, providing useful constraints for protein structure prediction. The method usually requires labor-intensive conjugation of nitroxide labels to multiple locations on the protein, one at a time. Here a computational procedure, based on protein sequence and simple secondary structure models, is presented to facilitate optimal placement of a minimum number of labels needed to determine the correct topology of a helical transmembrane protein. Tests on DsbB (four helices) using just one label lead to correct topology predictions in four of five cases, with the predicted structures <6 Å to the native structure. Benchmark results using simulated PRE data show that we can generally predict the correct topology for five and six to seven helices using two and three labels, respectively, with an average success rate of 76% and structures of similar precision. The results show promise in facilitating experimentally constrained structure prediction of membrane proteins.
authors.affiliation: Computational Systems Biology Lab, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, University of Georgia, Athens, GA 30602-4712, USA.
authors.forename: Huiling
authors.initials: H
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Ji
authors.forename: Victor
authors.initials: V
authors.lastname: Olman
authors.forename: Charles K
authors.initials: CK
authors.lastname: Mobley
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Liu
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: John H
authors.initials: JH
authors.lastname: Bushweller
authors.forename: James H
authors.initials: JH
authors.lastname: Prestegard
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results
chemical_list: D008565:Membrane Proteins