Systematic mappings of the effects of all possible mutations in a given protein sequence are routinely performed, with the aim of understanding protein structure-function and evolution. Most of these experiments indicate that the majority of amino acid substitutions are neutral. Our experimental system mimicked the manner by which protein sequences diverge in nature: a prolonged, gradual accumulation of mutations while retaining the protein¹s structure and function. Unlike previous mappings, the sequence-function Œheat map¹ derived from this experiment indicates that the fraction of deleterious mutations is in the order of 80% (dark to light blue) whereas the neutral mutations (white; ~15%), let alone beneficial mutations (~2%; in red), comprise a minority. Tawfik et al.
Image Credit: Tawfik et al.
Education
Informatics for RNA Sequencing: A Web Resource for Analysis on the Cloud
PLOS Computational Biology: published August 6, 2015 | https://doi.org/10.1371/journal.pcbi.1004393
Research Articles
Identifying Driver Genomic Alterations in Cancers by Searching Minimum-Weight, Mutually Exclusive Sets
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004257
An Optimal Free Energy Dissipation Strategy of the MinCDE Oscillator in Regulating Symmetric Bacterial Cell Division
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004351
Do Brain Networks Evolve by Maximizing Their Information Flow Capacity?
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004372
Flexible Modeling of Epidemics with an Empirical Bayes Framework
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004382
Inflow/Outflow Boundary Conditions for Particle-Based Blood Flow Simulations: Application to Arterial Bifurcations and Trees
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004410
Discovery of Drug Synergies in Gastric Cancer Cells Predicted by Logical Modeling
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004426
Analysis of Single Locus Trajectories for Extracting In Vivo Chromatin Tethering Interactions
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004433
Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004445
Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004454
Testing Foundations of Biological Scaling Theory Using Automated Measurements of Vascular Networks
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004455
Efficient Characterization of Parametric Uncertainty of Complex (Bio)chemical Networks
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004457
Functional Basis of Microorganism Classification
PLOS Computational Biology: published August 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004472
Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways
PLOS Computational Biology: published August 27, 2015 | https://doi.org/10.1371/journal.pcbi.1004321
Prediction of Functionally Important Phospho-Regulatory Events in Xenopus laevis Oocytes
PLOS Computational Biology: published August 27, 2015 | https://doi.org/10.1371/journal.pcbi.1004362
Asymmetric Evolutionary Games
PLOS Computational Biology: published August 26, 2015 | https://doi.org/10.1371/journal.pcbi.1004349
Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity
PLOS Computational Biology: published August 26, 2015 | https://doi.org/10.1371/journal.pcbi.1004422
Mechanism for Collective Cell Alignment in Myxococcus xanthus Bacteria
PLOS Computational Biology: published August 26, 2015 | https://doi.org/10.1371/journal.pcbi.1004474
Pluripotency, Differentiation, and Reprogramming: A Gene Expression Dynamics Model with Epigenetic Feedback Regulation
PLOS Computational Biology: published August 26, 2015 | https://doi.org/10.1371/journal.pcbi.1004476
Structure Learning in Bayesian Sensorimotor Integration
PLOS Computational Biology: published August 25, 2015 | https://doi.org/10.1371/journal.pcbi.1004369
Changes in Postural Syntax Characterize Sensory Modulation and Natural Variation of C. elegans Locomotion
PLOS Computational Biology: published August 21, 2015 | https://doi.org/10.1371/journal.pcbi.1004322
Tipping the Scale from Disorder to Alpha-helix: Folding of Amphiphilic Peptides in the Presence of Macroscopic and Molecular Interfaces
PLOS Computational Biology: published August 21, 2015 | https://doi.org/10.1371/journal.pcbi.1004328
Formation and Dynamics of Waves in a Cortical Model of Cholinergic Modulation
PLOS Computational Biology: published August 21, 2015 | https://doi.org/10.1371/journal.pcbi.1004449
Experimentally Verified Parameter Sets for Modelling Heterogeneous Neocortical Pyramidal-Cell Populations
PLOS Computational Biology: published August 20, 2015 | https://doi.org/10.1371/journal.pcbi.1004165
Impact of School Cycles and Environmental Forcing on the Timing of Pandemic Influenza Activity in Mexican States, May-December 2009
PLOS Computational Biology: published August 20, 2015 | https://doi.org/10.1371/journal.pcbi.1004337
Contribution of Sequence Motif, Chromatin State, and DNA Structure Features to Predictive Models of Transcription Factor Binding in Yeast
PLOS Computational Biology: published August 20, 2015 | https://doi.org/10.1371/journal.pcbi.1004418
A Three-Threshold Learning Rule Approaches the Maximal Capacity of Recurrent Neural Networks
PLOS Computational Biology: published August 20, 2015 | https://doi.org/10.1371/journal.pcbi.1004439
Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses
PLOS Computational Biology: published August 20, 2015 | https://doi.org/10.1371/journal.pcbi.1004458
The Interplay between Wnt Mediated Expansion and Negative Regulation of Growth Promotes Robust Intestinal Crypt Structure and Homeostasis
PLOS Computational Biology: published August 19, 2015 | https://doi.org/10.1371/journal.pcbi.1004285
Innate Immunity and the Inter-exposure Interval Determine the Dynamics of Secondary Influenza Virus Infection and Explain Observed Viral Hierarchies
PLOS Computational Biology: published August 18, 2015 | https://doi.org/10.1371/journal.pcbi.1004334
A Stochastic Multiscale Model That Explains the Segregation of Axonal Microtubules and Neurofilaments in Neurological Diseases
PLOS Computational Biology: published August 18, 2015 | https://doi.org/10.1371/journal.pcbi.1004406
Nonconsensus Protein Binding to Repetitive DNA Sequence Elements Significantly Affects Eukaryotic Genomes
PLOS Computational Biology: published August 18, 2015 | https://doi.org/10.1371/journal.pcbi.1004429
Unbiased Quantitative Models of Protein Translation Derived from Ribosome Profiling Data
PLOS Computational Biology: published August 14, 2015 | https://doi.org/10.1371/journal.pcbi.1004336
Controlled Measurement and Comparative Analysis of Cellular Components in E. coli Reveals Broad Regulatory Changes in Response to Glucose Starvation
PLOS Computational Biology: published August 14, 2015 | https://doi.org/10.1371/journal.pcbi.1004400
Curation of the Mammalian Palmitoylome Indicates a Pivotal Role for Palmitoylation in Diseases and Disorders of the Nervous System and Cancers
PLOS Computational Biology: published August 14, 2015 | https://doi.org/10.1371/journal.pcbi.1004405
The Role of Cell Volume in the Dynamics of Seizure, Spreading Depression, and Anoxic Depolarization
PLOS Computational Biology: published August 14, 2015 | https://doi.org/10.1371/journal.pcbi.1004414
Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations
PLOS Computational Biology: published August 14, 2015 | https://doi.org/10.1371/journal.pcbi.1004421
The Beta Cell in Its Cluster: Stochastic Graphs of Beta Cell Connectivity in the Islets of Langerhans
PLOS Computational Biology: published August 12, 2015 | https://doi.org/10.1371/journal.pcbi.1004423
A Bayesian Attractor Model for Perceptual Decision Making
PLOS Computational Biology: published August 12, 2015 | https://doi.org/10.1371/journal.pcbi.1004442
One Size Doesn't Fit All - RefEditor: Building Personalized Diploid Reference Genome to Improve Read Mapping and Genotype Calling in Next Generation Sequencing Studies
PLOS Computational Biology: published August 12, 2015 | https://doi.org/10.1371/journal.pcbi.1004448
A Spatially Detailed Model of Isometric Contraction Based on Competitive Binding of Troponin I Explains Cooperative Interactions between Tropomyosin and Crossbridges
PLOS Computational Biology: published August 11, 2015 | https://doi.org/10.1371/journal.pcbi.1004376
Manifold Based Optimization for Single-Cell 3D Genome Reconstruction
PLOS Computational Biology: published August 11, 2015 | https://doi.org/10.1371/journal.pcbi.1004396
Partial Unwrapping and Histone Tail Dynamics in Nucleosome Revealed by Coarse-Grained Molecular Simulations
PLOS Computational Biology: published August 11, 2015 | https://doi.org/10.1371/journal.pcbi.1004443
Exhaustive Analysis of a Genotype Space Comprising 1015 Central Carbon Metabolisms Reveals an Organization Conducive to Metabolic Innovation
PLOS Computational Biology: published August 7, 2015 | https://doi.org/10.1371/journal.pcbi.1004329
Knowledge-Based Analysis for Detecting Key Signaling Events from Time-Series Phosphoproteomics Data
PLOS Computational Biology: published August 7, 2015 | https://doi.org/10.1371/journal.pcbi.1004403
Modularity of Protein Folds as a Tool for Template-Free Modeling of Structures
PLOS Computational Biology: published August 7, 2015 | https://doi.org/10.1371/journal.pcbi.1004419
Irradiation of Neurons with High-Energy Charged Particles: An In Silico Modeling Approach
PLOS Computational Biology: published August 7, 2015 | https://doi.org/10.1371/journal.pcbi.1004428
Evolution of Self-Organized Task Specialization in Robot Swarms
PLOS Computational Biology: published August 6, 2015 | https://doi.org/10.1371/journal.pcbi.1004273
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Automatic Adaptation to Fast Input Changes in a Time-Invariant Neural Circuit
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