title: Improving prediction of helix-helix packing in membrane proteins using predicted contact numbers as restraints.
abstract: One of the challenging problems in tertiary structure prediction of helical membrane proteins (HMPs) is the determination of rotation of α-helices around the helix normal. Incorrect prediction of helix rotations substantially disrupts native residue-residue contacts while inducing only a relatively small effect on the overall fold. We previously developed a method for predicting residue contact numbers (CNs), which measure the local packing density of residues within the protein tertiary structure. In this study, we tested the idea of incorporating predicted CNs as restraints to guide the sampling of helix rotation. For a benchmark set of 15 HMPs with simple to rather complicated folds, the average contact recovery (CR) of best-sampled models was improved for all targets, the likelihood of sampling models with CR greater than 20% was increased for 13 targets, and the average RMSD100 of best-sampled models was improved for 12 targets. This study demonstrated that explicit incorporation of CNs as restraints improves the prediction of helix-helix packing. Proteins 2017; 85:1212-1221. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee, 37232.|Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, 37232.
authors.forename: Bian
authors.identifier: 0000-0002-8280-5018
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee, 37232.|Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, 37232.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Mendenhall
authors.affiliation: Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, 37232.
authors.forename: Elizabeth Dong
authors.initials: ED
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee, 37232.|Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, 37232.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Weiner
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee, 37232.|Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, 37232.
authors.forename: Axel W
authors.identifier: 0000-0003-0237-7365
authors.initials: AW
authors.lastname: Fischer
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee, 37232.|Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, 37232.
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry*; D019985:Benchmarking; D001665:Binding Sites; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary
chemical_list: D000596:Amino Acids; D008565:Membrane Proteins
keywords: contact number; de novo protein structure prediction; helical membrane protein; helix-helix packing; residue packing density