Why are proteins marginally stable?
Most globular proteins are marginally stable regardless of size or activity. The most common interpretation is that proteins must be marginally stable in order to function, and so marginal stability represents the results of positive selection. We consider the issue of marginal stability directly using model proteins and the dynamical aspects of protein evolution in populations. We find that the marginal stability of proteins is an inherent property of proteins due to the high dimensionality of the sequence space, without regard to protein function. In this way, marginal stability can result from neutral, non-adaptive evolution. By allowing evolving protein sub-populations with different stability requirements for functionality to complete, we find that marginally stable populations of proteins tend to dominate. Our results show that functionalities consistent with marginal stability have a strong evolutionary advantage, and might arise because of the natural tendency of proteins towards marginal stability.
A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains
A thermodynamic approach to the problem of stabilization of globular protein structure: a calorimetric study
Thermodynamic stability of annexin V E17G: equilibrium parameters from an irreversible unfolding reaction
Neutral networks in protein space: a computational study based on knowledge-based potentials of mean force
Engineering the independent folding of the subtilisin BPN' prodomain: analysis of two-state folding versus protein stability
Directed evolution of the suicide protein O⁶-alkylguanine-DNA alkyltransferase for increased reactivity results in an alkylated protein with exceptional stability
Thermal instability of ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) channel function: protection by single suppressor mutations and inhibiting channel activity
Dramatic destabilization of transmembrane helix interactions by features of natural membrane environments
Mechanical properties of bovine rhodopsin and bacteriorhodopsin: possible roles in folding and function
A fundamental protein property, thermodynamic stability, revealed solely from large-scale measurements of protein function
Binding constraints on the evolution of enzymes and signalling proteins: the important role of negative pleiotropy
PPARs in Human Neuroepithelial Tumors: PPAR Ligands as Anticancer Therapies for the Most Common Human Neuroepithelial Tumors
Peroxisome proliferator-activated receptors alpha, Beta, and gamma mRNA and protein expression in human fetal tissues
Expression Pattern of Peroxisome Proliferator-Activated Receptors in Rat Hippocampus following Cerebral Ischemia and Reperfusion Injury
PPARδ agonist GW501516 inhibits PDGF-stimulated pulmonary arterial smooth muscle cell function related to pathological vascular remodeling
In silico identification of functional divergence between the multiple groEL gene paralogs in Chlamydiae
Neutral genetic drift can alter promiscuous protein functions, potentially aiding functional evolution
A first-principles model of early evolution: emergence of gene families, species, and preferred protein folds
Revisiting the myths of protein interior: studying proteins with mass-fractal hydrophobicity-fractal and polarizability-fractal dimensions
A computational-experimental approach identifies mutations that enhance surface expression of an oseltamivir-resistant influenza neuraminidase
Comparative metaproteomics and diversity analysis of human intestinal microbiota testifies for its temporal stability and expression of core functions
Neutral evolution of proteins: The superfunnel in sequence space and its relation to mutational robustness
Detecting selection on protein stability through statistical mechanical models of folding and evolution
Contribution of selection for protein folding stability in shaping the patterns of polymorphisms in coding regions
Synthesis, docking and evaluation of antioxidant and antimicrobial activities of novel 1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-6-yl)selenopheno[2,3-d]pyrimidines
A convenient synthesis and molecular modeling study of novel pyrazolo[3,4-d]pyrimidine and pyrazole derivatives as anti-tumor agents
Fast, cheap and out of control--Insights into thermodynamic and informatic constraints on natural protein sequences from de novo protein design
Multiple global suppressors of protein stability defects facilitate the evolution of extended-spectrum TEM β-lactamases
A stability pattern of protein hydrophobic mutations that reflects evolutionary structural optimization
Funnel-like organization in sequence space determines the distributions of protein stability and folding rate preferred by evolution
In-Depth High-Throughput Screening of Protein Engineering Libraries by Split-GFP Direct Crude Cell Extract Data Normalization
Directed evolution of a histone acetyltransferase--enhancing thermostability, whilst maintaining catalytic activity and substrate specificity
Reconstructed Ancestral Enzymes Impose a Fitness Cost upon Modern Bacteria Despite Exhibiting Favourable Biochemical Properties
Using a second-order differential model to fit data without baselines in protein isothermal chemical denaturation
Evaluation of models for the evolution of protein sequences and functions under structural constraint
Effect of sorbitol and glycerol on the stability of trypsin and difference between their stabilization effects in the various solvents
Mutational studies on resurrected ancestral proteins reveal conservation of site-specific amino acid preferences throughout evolutionary history
Residue mutations and their impact on protein structure and function: detecting beneficial and pathogenic changes
Merging molecular mechanism and evolution: theory and computation at the interface of biophysics and evolutionary population genetics
Stabilization of an α/β-Hydrolase by Introducing Proline Residues: Salicylic Acid Binding Protein 2 from Tobacco
Efficient and robust analysis of biomacromolecular flexibility using ensembles of network topologies based on fuzzy noncovalent constraints
Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently
Phytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations
Denatured states of yeast cytochrome c induced by heat and guanidinium chloride are structurally and thermodynamically different
Network models of TEM β-lactamase mutations coevolving under antibiotic selection show modular structure and anticipate evolutionary trajectories
Selection for Protein Kinetic Stability Connects Denaturation Temperatures to Organismal Temperatures and Provides Clues to Archaean Life
Thermal stabilization of dihydrofolate reductase using monte carlo unfolding simulations and its functional consequences
Prediction of protein-protein interface sequence diversity using flexible backbone computational protein design
Existence of metastable intermediate lysozyme conformation highlights the role of alcohols in altering protein stability
Plasminogen activator inhibitor-2 is highly tolerant to P8 residue substitution--implications for serpin mechanistic model and prediction of nsSNP activities
A Natural Mutation in Helix 5 of the Ligand Binding Domain of Glucocorticoid Receptor Enhances Receptor-Ligand Interaction
Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein
Predicting the Effect of Amino Acid Single-Point Mutations on Protein Stability-Large-Scale Validation of MD-Based Relative Free Energy Calculations
Direct examination of the relevance for folding, binding and electron transfer of a conserved protein folding intermediate
Temperature evolution of Trp-cage folding pathways: An analysis by dividing the probability flux field into stream tubes
Structure-Related Differences between Cytochrome Oxidase I Proteins in a Stable Heteroplasmic Mitochondrial System
Role of an N-terminal extension in stability and catalytic activity of a hyperthermostable α/β hydrolase fold esterase
Beyond Stability Constraints: A Biophysical Model of Enzyme Evolution with Selection on Stability and Activity
Stability constraints and protein evolution: the role of chain length, composition and disulfide bonds
SodaPop: a forward simulation suite for the evolutionary dynamics of asexual populations on protein fitness landscapes
In silico thermodynamic stability of mammalian adaptation and virulence determinants in polymerase complex proteins of H9N2 virus
Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites
Fitness effects but no temperature-mediated balancing selection at the polymorphic Adh gene of Drosophila melanogaster
Overview of protein folding mechanisms: experimental and theoretical approaches to probing energy landscapes
Selection on metabolic pathway function in the presence of mutation-selection-drift balance leads to rate-limiting steps that are not evolutionarily stable
Extreme stability in de novo-designed repeat arrays is determined by unusually stable short-range interactions
Evolutionary Processes and Biophysical Mechanisms: Revisiting Why Evolved Proteins Are Marginally Stable
Superfunneled Energy Landscape of Protein Evolution Unifies the Principles of Protein Evolution, Folding, and Design
Inducing secondary structural interplays between scallop muscle proteins and soy proteins to form soluble composites
The Marginal Stability of Proteins: How the Jiggling and Wiggling of Atoms is Connected to Neutral Evolution
Stabilization of a nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator yields insight into disease-causing mutations
Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.
Synthetic Genetic Array Analysis
Synthetic genetic arrays allow the systematic examination of genetic interactions. Here is the latest research focusing on synthetic genetic arrays and their analyses.
Congenital hyperinsulinism is caused by genetic mutations resulting in excess insulin secretion from beta cells of the pancreas. Here is the latest research.
Neural Activity: Imaging
Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.
Chronic Fatigue Syndrome
Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.
Epigenetic memory refers to the heritable genetic changes that are not explained by the DNA sequence. Find the latest research on epigenetic memory here.
Cell Atlas of the Human Eye
Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.
Femoral Neoplasms are bone tumors that arise in the femur. Discover the latest research on femoral neoplasms here.
STING Receptor Agonists
Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.