September 2014

Drugs are typically developed to modulate the function of specific proteins, which are directly associated with particular disease states. Nonetheless, protein-drug interactions are rather promiscuous and the majority of pharmaceuticals exhibit activity against multiple, often unrelated targets; for instance, ATP-dependent DNA ligase and histamine N-methyltransferase shown here bind the same compound. To detect those binding sites having the capability to bind similar molecules, Michal Brylinski developed eMatchSite, which constructs local sequence order-independent alignments using computer-generated protein models. This approach opens up the possibility to investigate drug-protein interactions for complete proteomes with prospective systems-level applications in polypharmacology and rational drug repositioning.

Image Credit: Michal Brylinski

Editorial

Ten Simple Rules for Better Figures

Nicolas P. Rougier, Michael Droettboom, Philip E. Bourne

PLOS Computational Biology: published September 11, 2014 | https://doi.org/10.1371/journal.pcbi.1003833

Topic Page

Multi-state Modeling of Biomolecules

Melanie I. Stefan, Thomas M. Bartol, Terrence J. Sejnowski, Mary B. Kennedy

PLOS Computational Biology: published September 25, 2014 | https://doi.org/10.1371/journal.pcbi.1003844

Research Articles

Stochastic Dynamics of Interacting Haematopoietic Stem Cell Niche Lineages

Tamás Székely Jr, Kevin Burrage, Marc Mangel, Michael B. Bonsall

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003794

Data-Derived Modeling Characterizes Plasticity of MAPK Signaling in Melanoma

Marti Bernardo-Faura, Stefan Massen, Christine S. Falk, Nathan R. Brady, Roland Eils

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003795

Dynamic Conformational Change Regulates the Protein-DNA Recognition: An Investigation on Binding of a Y-Family Polymerase to Its Target DNA

Xiakun Chu, Fei Liu, Brian A. Maxwell, Yong Wang, Zucai Suo, Haijun Wang, Wei Han, Jin Wang

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003804

Emergence of Assortative Mixing between Clusters of Cultured Neurons

Sara Teller, Clara Granell, Manlio De Domenico, Jordi Soriano, Sergio Gómez, Alex Arenas

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003796

Seasonally Dependent Relationships between Indicators of Malaria Transmission and Disease Provided by Mathematical Model Simulations

Erin M. Stuckey, Thomas Smith, Nakul Chitnis

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003812

Evolution of the F₀F₁ ATP Synthase Complex in Light of the Patchy Distribution of Different Bioenergetic Pathways across Prokaryotes

Vassiliki Lila Koumandou, Sophia Kossida

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003821

Phase Transitions in the Multi-cellular Regulatory Behavior of Pancreatic Islet Excitability

Thomas H. Hraha, Matthew J. Westacott, Marina Pozzoli, Aleena M. Notary, P. Mason McClatchey, Richard K. P. Benninger

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003819

Pep2Path: Automated Mass Spectrometry-Guided Genome Mining of Peptidic Natural Products

Marnix H. Medema, Yared Paalvast, Don D. Nguyen, Alexey Melnik, Pieter C. Dorrestein, Eriko Takano, Rainer Breitling

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003822

Torsion-Mediated Interaction between Adjacent Genes

Sam Meyer, Guillaume Beslon

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003785

A Probabilistic Model to Predict Clinical Phenotypic Traits from Genome Sequencing

Yun-Ching Chen, Christopher Douville, Cheng Wang, Noushin Niknafs, Grace Yeo, Violeta Beleva-Guthrie, Hannah Carter, Peter D. Stenson, David N. Cooper, Biao Li, Sean Mooney, Rachel Karchin

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003825

Revealing Molecular Mechanisms by Integrating High-Dimensional Functional Screens with Protein Interaction Data

Angela Simeone, Giovanni Marsico, Claudio Collinet, Thierry Galvez, Yannis Kalaidzidis, Marino Zerial, Andreas Beyer

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003801

A Peptide-Based Method for ¹³C Metabolic Flux Analysis in Microbial Communities

Amit Ghosh, Jerome Nilmeier, Daniel Weaver, Paul D. Adams, Jay D. Keasling, Aindrila Mukhopadhyay, Christopher J. Petzold, Héctor García Martín

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003827

Baseline CD4⁺ T Cell Counts Correlates with HIV-1 Synonymous Rate in HLA-B*5701 Subjects with Different Risk of Disease Progression

Melissa M. Norström, Nazle M. Veras, Wei Huang, Mattia C. F. Proper, Jennifer Cook, Wendy Hartogensis, Frederick M. Hecht, Annika C. Karlsoon, Marco Salemi

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003830

Inferring on the Intentions of Others by Hierarchical Bayesian Learning

Andreea O. Diaconescu, Christoph Mathys, Lilian A. E. Weber, Jean Daunizeau, Lars Kasper, Ekaterina I. Lomakina, Ernst Fehr, Klaas E. Stephan

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003810

Strategies for Controlling Non-Transmissible Infection Outbreaks Using a Large Human Movement Data Set

Penelope A. Hancock, Yasmin Rehman, Ian M. Hall, Obaghe Edeghere, Leon Danon, Thomas A. House, Matthew J. Keeling

PLOS Computational Biology: published September 11, 2014 | https://doi.org/10.1371/journal.pcbi.1003809

PTEN Hopping on the Cell Membrane Is Regulated via a Positively-Charged C2 Domain

Masato Yasui, Satomi Matsuoka, Masahiro Ueda

PLOS Computational Biology: published September 11, 2014 | https://doi.org/10.1371/journal.pcbi.1003817

Principal Component Analysis Characterizes Shared Pathogenetics from Genome-Wide Association Studies

Diana Chang, Alon Keinan

PLOS Computational Biology: published September 11, 2014 | https://doi.org/10.1371/journal.pcbi.1003820

Communication Routes in ARID Domains between Distal Residues in Helix 5 and the DNA-Binding Loops

Gaetano Invernizzi, Matteo Tiberti, Matteo Lambrughi, Kresten Lindorff-Larsen, Elena Papaleo

PLOS Computational Biology: published September 4, 2014 | https://doi.org/10.1371/journal.pcbi.1003744

Determining Individual Variation in Growth and Its Implication for Life-History and Population Processes Using the Empirical Bayes Method

Simone Vincenzi, Marc Mangel, Alain J. Crivelli, Stephan Munch, Hans J. Skaug

PLOS Computational Biology: published September 11, 2014 | https://doi.org/10.1371/journal.pcbi.1003828

SANTA: Quantifying the Functional Content of Molecular Networks

Alex J. Cornish, Florian Markowetz

PLOS Computational Biology: published September 11, 2014 | https://doi.org/10.1371/journal.pcbi.1003808

Mathematical Modeling of Bacterial Kinetics to Predict the Impact of Antibiotic Colonic Exposure and Treatment Duration on the Amount of Resistant Enterobacteria Excreted

Thu Thuy Nguyen, Jeremie Guedj, Elisabeth Chachaty, Jean de Gunzburg, Antoine Andremont, France Mentré

PLOS Computational Biology: published September 11, 2014 | https://doi.org/10.1371/journal.pcbi.1003840

The Time Scale of Evolutionary Innovation

Krishnendu Chatterjee, Andreas Pavlogiannis, Ben Adlam, Martin A. Nowak

PLOS Computational Biology: published September 11, 2014 | https://doi.org/10.1371/journal.pcbi.1003818

Molecular Simulation-Based Structural Prediction of Protein Complexes in Mass Spectrometry: The Human Insulin Dimer

Jinyu Li, Giulia Rossetti, Jens Dreyer, Simone Raugei, Emiliano Ippoliti, Bernhard Lüscher, Paolo Carloni

PLOS Computational Biology: published September 11, 2014 | https://doi.org/10.1371/journal.pcbi.1003838

The Structural Basis of ATP as an Allosteric Modulator

Shaoyong Lu, Wenkang Huang, Qi Wang, Qiancheng Shen, Shuai Li, Ruth Nussinov, Jian Zhang

PLOS Computational Biology: published September 11, 2014 | https://doi.org/10.1371/journal.pcbi.1003831

Geometry Shapes Evolution of Early Multicellularity

Eric Libby, William Ratcliff, Michael Travisano, Ben Kerr

PLOS Computational Biology: published September 18, 2014 | https://doi.org/10.1371/journal.pcbi.1003803

NESmapper: Accurate Prediction of Leucine-Rich Nuclear Export Signals Using Activity-Based Profiles

Shunichi Kosugi, Hiroshi Yanagawa, Ryohei Terauchi, Satoshi Tabata

PLOS Computational Biology: published September 18, 2014 | https://doi.org/10.1371/journal.pcbi.1003841

Spatial Heterogeneity and Peptide Availability Determine CTL Killing Efficiency In Vivo

Thea Hogan, Ulrich Kadolsky, Sim Tung, Benedict Seddon, Andrew Yates

PLOS Computational Biology: published September 18, 2014 | https://doi.org/10.1371/journal.pcbi.1003805

Allele-Specific Network Reveals Combinatorial Interaction That Transcends Small Effects in Psoriasis GWAS

Sharlee Climer, Alan R. Templeton, Weixiong Zhang

PLOS Computational Biology: published September 18, 2014 | https://doi.org/10.1371/journal.pcbi.1003766

Environmental Statistics and Optimal Regulation

David A. Sivak, Matt Thomson

PLOS Computational Biology: published September 25, 2014 | https://doi.org/10.1371/journal.pcbi.1003826

eMatchSite: Sequence Order-Independent Structure Alignments of Ligand Binding Pockets in Protein Models

Michal Brylinski

PLOS Computational Biology: published September 18, 2014 | https://doi.org/10.1371/journal.pcbi.1003829

A Novel Model to Combine Clinical and Pathway-Based Transcriptomic Information for the Prognosis Prediction of Breast Cancer

Sijia Huang, Cameron Yee, Travers Ching, Herbert Yu, Lana X. Garmire

PLOS Computational Biology: published September 18, 2014 | https://doi.org/10.1371/journal.pcbi.1003851

Examining Variable Domain Orientations in Antigen Receptors Gives Insight into TCR-Like Antibody Design

James Dunbar, Bernhard Knapp, Angelika Fuchs, Jiye Shi, Charlotte M. Deane

PLOS Computational Biology: published September 18, 2014 | https://doi.org/10.1371/journal.pcbi.1003852

Pupil-Linked Arousal Determines Variability in Perceptual Decision Making

Peter R. Murphy, Joachim Vandekerckhove, Sander Nieuwenhuis

PLOS Computational Biology: published September 18, 2014 | https://doi.org/10.1371/journal.pcbi.1003854

Synchronization of Isolated Downstates (K-Complexes) May Be Caused by Cortically-Induced Disruption of Thalamic Spindling

Rachel A. Mak-McCully, Stephen R. Deiss, Burke Q. Rosen, Ki-Young Jung, Terrence J. Sejnowski, Hélène Bastuji, Marc Rey, Sydney S. Cash, Maxim Bazhenov, Eric Halgren

PLOS Computational Biology: published September 25, 2014 | https://doi.org/10.1371/journal.pcbi.1003855

A Systems Approach to Predict Oncometabolites via Context-Specific Genome-Scale Metabolic Networks

Hojung Nam, Miguel Campodonico, Aarash Bordbar, Daniel R. Hyduke, Sangwoo Kim, Daniel C. Zielinski, Bernhard O. Palsson

PLOS Computational Biology: published September 18, 2014 | https://doi.org/10.1371/journal.pcbi.1003837

Multidimensional Epistasis and the Transitory Advantage of Sex

Stefan Nowak, Johannes Neidhart, Ivan G. Szendro, Joachim Krug

PLOS Computational Biology: published September 18, 2014 | https://doi.org/10.1371/journal.pcbi.1003836

Characterizing Protein Interactions Employing a Genome-Wide siRNA Cellular Phenotyping Screen

Apichat Suratanee, Martin H. Schaefer, Matthew J. Betts, Zita Soons, Heiko Mannsperger, Nathalie Harder, Marcus Oswald, Markus Gipp, Ellen Ramminger, Guillermo Marcus, Reinhard Männer, Karl Rohr, Erich Wanker, Robert B. Russell, Miguel A. Andrade-Navarro, Roland Eils, Rainer König

PLOS Computational Biology: published September 25, 2014 | https://doi.org/10.1371/journal.pcbi.1003814

Identifying Cell Types from Spatially Referenced Single-Cell Expression Datasets

Jean-Baptiste Pettit, Raju Tomer, Kaia Achim, Sylvia Richardson, Lamiae Azizi, John Marioni

PLOS Computational Biology: published September 25, 2014 | https://doi.org/10.1371/journal.pcbi.1003824

A Bayesian Framework to Identify Methylcytosines from High-Throughput Bisulfite Sequencing Data

Qing Xie, Qi Liu, Fengbiao Mao, Wanshi Cai, Honghu Wu, Mingcong You, Zhen Wang, Bingyu Chen, Zhong Sheng Sun, Jinyu Wu

PLOS Computational Biology: published September 25, 2014 | https://doi.org/10.1371/journal.pcbi.1003853

IDEPI: Rapid Prediction of HIV-1 Antibody Epitopes and Other Phenotypic Features from Sequence Data Using a Flexible Machine Learning Platform

N. Lance Hepler, Konrad Scheffler, Steven Weaver, Ben Murrell, Douglas D. Richman, Dennis R. Burton, Pascal Poignard, Davey M. Smith, Sergei L. Kosakovsky Pond

PLOS Computational Biology: published September 25, 2014 | https://doi.org/10.1371/journal.pcbi.1003842

Correction

Correction: Structure-Based Druggability Assessment of the Mammalian Structural Proteome with Inclusion of Light Protein Flexibility

The PLOS Computational Biology Staff

PLOS Computational Biology: published September 9, 2014 | https://doi.org/10.1371/journal.pcbi.1003875

Cover

Matching drug binding pockets in protein models using sequence order-independent structure alignments.

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