title: Accurate Prediction of Contact Numbers for Multi-Spanning Helical Membrane Proteins.
abstract: Prediction of the three-dimensional (3D) structures of proteins by computational methods is acknowledged as an unsolved problem. Accurate prediction of important structural characteristics such as contact number is expected to accelerate the otherwise slow progress being made in the prediction of 3D structure of proteins. Here, we present a dropout neural network-based method, TMH-Expo, for predicting the contact number of transmembrane helix (TMH) residues from sequence. Neuronal dropout is a strategy where certain neurons of the network are excluded from back-propagation to prevent co-adaptation of hidden-layer neurons. By using neuronal dropout, overfitting was significantly reduced and performance was noticeably improved. For multi-spanning helical membrane proteins, TMH-Expo achieved a remarkable Pearson correlation coefficient of 0.69 between predicted and experimental values and a mean absolute error of only 1.68. In addition, among those membrane protein-membrane protein interface residues, 76.8% were correctly predicted. Mapping of predicted contact numbers onto structures indicates that contact numbers predicted by TMH-Expo reflect the exposure patterns of TMHs and reveal membrane protein-membrane protein interfaces, reinforcing the potential of predicted contact numbers to be used as restraints for 3D structure prediction and protein-protein docking. TMH-Expo can be accessed via a Web server at www.meilerlab.org .
authors.affiliation: Department of Chemistry, Vanderbilt University , Nashville, Tennessee 37232, United States.|Center for Structural Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: Bian
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Chemistry, Vanderbilt University , Nashville, Tennessee 37232, United States.|Center for Structural Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Mendenhall
authors.affiliation: Center for Structural Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: Elizabeth Dong
authors.initials: ED
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry, Vanderbilt University , Nashville, Tennessee 37232, United States.|Center for Structural Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Weiner
authors.affiliation: Department of Chemistry, Vanderbilt University , Nashville, Tennessee 37232, United States.|Center for Structural Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: Axel W
authors.initials: AW
authors.lastname: Fischer
authors.affiliation: Department of Chemistry, Vanderbilt University , Nashville, Tennessee 37232, United States.|Center for Structural Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
mesh_terms: D008565:Membrane Proteins / Q000737:chemistry*; D011487:Protein Conformation; D012997:Solvents / Q000737:chemistry
chemical_list: D008565:Membrane Proteins; D012997:Solvents