March 2009

For many years, it has been known that mutations in the human huntingtin protein are responsible for Huntington chorea, a neurodegenerative disease. However, very little is known about the structure and function of this long protein. Using a computational method on a sequence alignment of huntingtin with its orthologs (output shown in the background), we have predicted that this protein contains three elongated domains (alpha-rods, yellow cylinders) that are involved in intramolecular (left) and intermolecular (right) interactions (see Palidwor et al., doi:10.1371/journal.pcbi.1000304). This work opens avenues for further characterization of huntingtin and other proteins with alpha-rods.

Image Credit: Cartoon created using Google SketchUp and BiasViz by Miguel Andrade-Navarro (Max Delbrück Center for Molecular Medicine, Germany).

Review

A Proposal for a Coordinated Effort for the Determination of Brainwide Neuroanatomical Connectivity in Model Organisms at a Mesoscopic Scale

Jason W. Bohland, Caizhi Wu, Helen Barbas, Hemant Bokil, Mihail Bota, Hans C. Breiter, Hollis T. Cline, John C. Doyle, Peter J. Freed, Ralph J. Greenspan, Suzanne N. Haber, Michael Hawrylycz, Daniel G. Herrera, Claus C. Hilgetag, Z. Josh Huang, Allan Jones, Edward G. Jones, Harvey J. Karten, David Kleinfeld, Rolf Kötter, Henry A. Lester, John M. Lin, Brett D. Mensh, Shawn Mikula, Jaak Panksepp, Joseph L. Price, Joseph Safdieh, Clifford B. Saper, Nicholas D. Schiff, Jeremy D. Schmahmann, Bruce W. Stillman, Karel Svoboda, Larry W. Swanson, Arthur W. Toga, David C. Van Essen, James D. Watson, Partha P. Mitra

PLOS Computational Biology: published March 27, 2009 | https://doi.org/10.1371/journal.pcbi.1000334

Research Articles

Robustness in Glyoxylate Bypass Regulation

Guy Shinar, Joshua D. Rabinowitz, Uri Alon

PLOS Computational Biology: published March 6, 2009 | https://doi.org/10.1371/journal.pcbi.1000297

Steady-State Kinetic Modeling Constrains Cellular Resting States and Dynamic Behavior

Jeremy E. Purvis, Ravi Radhakrishnan, Scott L. Diamond

PLOS Computational Biology: published March 6, 2009 | https://doi.org/10.1371/journal.pcbi.1000298

Alu Exonization Events Reveal Features Required for Precise Recognition of Exons by the Splicing Machinery

Schraga Schwartz, Nurit Gal-Mark, Nir Kfir, Ram Oren, Eddo Kim, Gil Ast

PLOS Computational Biology: published March 6, 2009 | https://doi.org/10.1371/journal.pcbi.1000300

Understanding Pitch Perception as a Hierarchical Process with Top-Down Modulation

Emili Balaguer-Ballester, Nicholas R. Clark, Martin Coath, Katrin Krumbholz, Susan L. Denham

PLOS Computational Biology: published March 6, 2009 | https://doi.org/10.1371/journal.pcbi.1000301

The Modulation Transfer Function for Speech Intelligibility

Taffeta M. Elliott, Frédéric E. Theunissen

PLOS Computational Biology: published March 6, 2009 | https://doi.org/10.1371/journal.pcbi.1000302

Alignment and Prediction of cis-Regulatory Modules Based on a Probabilistic Model of Evolution

Xin He, Xu Ling, Saurabh Sinha

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000299

Canalization of Gene Expression and Domain Shifts in the Drosophila Blastoderm by Dynamical Attractors

Manu, Svetlana Surkova, Alexander V. Spirov, Vitaly V. Gursky, Hilde Janssens, Ah-Ram Kim, Ovidiu Radulescu, Carlos E. Vanario-Alonso, David H. Sharp, Maria Samsonova, John Reinitz

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000303

Detection of Alpha-Rod Protein Repeats Using a Neural Network and Application to Huntingtin

Gareth A. Palidwor, Sergey Shcherbinin, Matthew R. Huska, Tamas Rasko, Ulrich Stelzl, Anup Arumughan, Raphaele Foulle, Pablo Porras, Luis Sanchez-Pulido, Erich E. Wanker, Miguel A. Andrade-Navarro

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000304

Timing the Emergence of Resistance to Anti-HIV Drugs with Large Genetic Barriers

Pankhuri Arora, Narendra M. Dixit

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000305

Mechanical Network in Titin Immunoglobulin from Force Distribution Analysis

Wolfram Stacklies, M. Cristina Vega, Matthias Wilmanns, Frauke Gräter

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000306

Probabilistic Interaction Network of Evidence Algorithm and its Application to Complete Labeling of Peak Lists from Protein NMR Spectroscopy

Arash Bahrami, Amir H. Assadi, John L. Markley, Hamid R. Eghbalnia

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000307

GrowMatch: An Automated Method for Reconciling In Silico/In Vivo Growth Predictions

Vinay Satish Kumar, Costas D. Maranas

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000308

Mechanism of Action of Cyclophilin A Explored by Metadynamics Simulations

Vanessa Leone, Gianluca Lattanzi, Carla Molteni, Paolo Carloni

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000309

Cortical Factor Feedback Model for Cellular Locomotion and Cytofission

Shin I. Nishimura, Masahiro Ueda, Masaki Sasai

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000310

Genome-Scale Reconstruction of Escherichia coli's Transcriptional and Translational Machinery: A Knowledge Base, Its Mathematical Formulation, and Its Functional Characterization

Ines Thiele, Neema Jamshidi, Ronan M. T. Fleming, Bernhard Ø. Palsson

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000312

Toward a Detailed Description of the Thermally Induced Dynamics of the Core Promoter

Boian S. Alexandrov, Vladimir Gelev, Sang Wook Yoo, Alan R. Bishop, Kim Ø. Rasmussen, Anny Usheva

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000313

Sm/Lsm Genes Provide a Glimpse into the Early Evolution of the Spliceosome

Stella Veretnik, Christopher Wills, Philippe Youkharibache, Ruben E. Valas, Philip E. Bourne

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000315

Intrinsic Disorder in Protein Interactions: Insights From a Comprehensive Structural Analysis

Jessica H. Fong, Benjamin A. Shoemaker, Sergiy O. Garbuzynskiy, Michail Y. Lobanov, Oxana V. Galzitskaya, Anna R. Panchenko

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000316

Robust Detection and Genotyping of Single Feature Polymorphisms from Gene Expression Data

Minghui Wang, Xiaohua Hu, Gang Li, Lindsey J. Leach, Elena Potokina, Arnis Druka, Robbie Waugh, Michael J. Kearsey, Zewei Luo

PLOS Computational Biology: published March 13, 2009 | https://doi.org/10.1371/journal.pcbi.1000317

Using Network Component Analysis to Dissect Regulatory Networks Mediated by Transcription Factors in Yeast

Chun Ye, Simon J. Galbraith, James C. Liao, Eleazar Eskin

PLOS Computational Biology: published March 20, 2009 | https://doi.org/10.1371/journal.pcbi.1000311

Broadband Criticality of Human Brain Network Synchronization

Manfred G. Kitzbichler, Marie L. Smith, Søren R. Christensen, Ed Bullmore

PLOS Computational Biology: published March 20, 2009 | https://doi.org/10.1371/journal.pcbi.1000314

Accurate Detection of Recombinant Breakpoints in Whole-Genome Alignments

Oscar Westesson, Ian Holmes

PLOS Computational Biology: published March 20, 2009 | https://doi.org/10.1371/journal.pcbi.1000318

Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles

Pedro M. B. M. Coelho, Armindo Salvador, Michael A. Savageau

PLOS Computational Biology: published March 20, 2009 | https://doi.org/10.1371/journal.pcbi.1000319

On the Growth of Scientific Knowledge: Yeast Biology as a Case Study

Xionglei He, Jianzhi Zhang

PLOS Computational Biology: published March 20, 2009 | https://doi.org/10.1371/journal.pcbi.1000320

Computational Model of the Insect Pheromone Transduction Cascade

Yuqiao Gu, Philippe Lucas, Jean-Pierre Rospars

PLOS Computational Biology: published March 20, 2009 | https://doi.org/10.1371/journal.pcbi.1000321

Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis

Matthew A. Hibbs, Chad L. Myers, Curtis Huttenhower, David C. Hess, Kai Li, Amy A. Caudy, Olga G. Troyanskaya

PLOS Computational Biology: published March 20, 2009 | https://doi.org/10.1371/journal.pcbi.1000322

Modeling Signal Propagation Mechanisms and Ligand-Based Conformational Dynamics of the Hsp90 Molecular Chaperone Full-Length Dimer

Giulia Morra, Gennady Verkhivker, Giorgio Colombo

PLOS Computational Biology: published March 20, 2009 | https://doi.org/10.1371/journal.pcbi.1000323

Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics

Barry J. Grant, Alemayehu A. Gorfe, J. Andrew McCammon

PLOS Computational Biology: published March 20, 2009 | https://doi.org/10.1371/journal.pcbi.1000325

A Systems Approach Uncovers Restrictions for Signal Interactions Regulating Genome-wide Responses to Nutritional Cues in Arabidopsis

Gabriel Krouk, Daniel Tranchina, Laurence Lejay, Alexis A. Cruikshank, Dennis Shasha, Gloria M. Coruzzi, Rodrigo A. Gutiérrez

PLOS Computational Biology: published March 20, 2009 | https://doi.org/10.1371/journal.pcbi.1000326

Estimation of Thalamocortical and Intracortical Network Models from Joint Thalamic Single-Electrode and Cortical Laminar-Electrode Recordings in the Rat Barrel System

Patrick Blomquist, Anna Devor, Ulf G. Indahl, Istvan Ulbert, Gaute T. Einevoll, Anders M. Dale

PLOS Computational Biology: published March 27, 2009 | https://doi.org/10.1371/journal.pcbi.1000328

“I Look in Your Eyes, Honey”: Internal Face Features Induce Spatial Frequency Preference for Human Face Processing

Matthias S. Keil

PLOS Computational Biology: published March 27, 2009 | https://doi.org/10.1371/journal.pcbi.1000329

Cross-Over between Discrete and Continuous Protein Structure Space: Insights into Automatic Classification and Networks of Protein Structures

Alberto Pascual-García, David Abia, Ángel R. Ortiz, Ugo Bastolla

PLOS Computational Biology: published March 27, 2009 | https://doi.org/10.1371/journal.pcbi.1000331

Cover

Nearing the structure of the human huntingtin protein.

Review

Research Articles

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