Protein evolution
View article
ModelTest-NG: A New and Scalable Tool for the Selection of DNA and Protein Evolutionary Models Open
ModelTest-NG is a reimplementation from scratch of jModelTest and ProtTest, two popular tools for selecting the best-fit nucleotide and amino acid substitution models, respectively. ModelTest-NG is one to two orders of magnitude faster tha…
View article
Protein structure determination using metagenome sequence data Open
Filling in the protein fold picture Fewer than a third of the 14,849 known protein families have at least one member with an experimentally determined structure. This leaves more than 5000 protein families with no structural information. P…
View article
Large-scale determination of previously unsolved protein structures using evolutionary information Open
The prediction of the structures of proteins without detectable sequence similarity to any protein of known structure remains an outstanding scientific challenge. Here we report significant progress in this area. We first describe de novo …
View article
ConSurf‐DB: An accessible repository for the evolutionary conservation patterns of the majority of PDB proteins Open
Patterns observed by examining the evolutionary relationships among proteins of common origin can reveal the structural and functional importance of specific residue positions. In particular, amino acids that are highly conserved (i.e., th…
View article
Consensus protein design Open
A popular and successful strategy in semi-rational design of protein stability is the use of evolutionary information encapsulated in homologous protein sequences. Consensus design is based on the hypothesis that at a given position, the r…
View article
Contingency and entrenchment in protein evolution under purifying selection Open
Significance How large a role does history play in evolution? Do later events depend critically on specific earlier events, or do all events occur more or less independently? If a change occurs early in evolution, does it become easier or …
View article
On the Causes of Evolutionary Transition:Transversion Bias Open
A pattern in which nucleotide transitions are favored several fold over transversions is common in molecular evolution. When this pattern occurs among amino acid replacements, explanations often invoke an effect of selection, on the ground…
View article
How Pairwise Coevolutionary Models Capture the Collective Residue Variability in Proteins? Open
Global coevolutionary models of homologous protein families, as constructed by direct coupling analysis (DCA), have recently gained popularity in particular due to their capacity to accurately predict residue-residue contacts from sequence…
View article
Biophysical Models of Protein Evolution: Understanding the Patterns of Evolutionary Sequence Divergence Open
For decades, rates of protein evolution have been interpreted in terms of the vague concept of functional importance. Slowly evolving proteins or sites within proteins were assumed to be more functionally important and thus subject to stro…
View article
Pervasive contingency and entrenchment in a billion years of Hsp90 evolution Open
Significance When mutations within a protein change each other’s functional effects—a phenomenon called epistasis—the paths available to evolution at any moment in time depend on the specific set of changes that previously occurred in the …
View article
Complex evolutionary footprints revealed in an analysis of reused protein segments of diverse lengths Open
Significance We question a central paradigm: namely, that the protein domain is the “atomic unit” of evolution. In conflict with the current textbook view, our results unequivocally show that duplication of protein segments happens both ab…
View article
Contingency and chance erase necessity in the experimental evolution of ancestral proteins Open
The roles of chance, contingency, and necessity in evolution are unresolved because they have never been assessed in a single system or on timescales relevant to historical evolution. We combined ancestral protein reconstruction and a new …
View article
Protein threading using residue co-variation and deep learning Open
Motivation Template-based modeling, including homology modeling and protein threading, is a popular method for protein 3D structure prediction. However, alignment generation and template selection for protein sequences without close templa…
View article
Mechanisms of protein evolution Open
How do proteins evolve? How do changes in sequence mediate changes in protein structure, and in turn in function? This question has multiple angles, ranging from biochemistry and biophysics to evolutionary biology. This review provides a b…
View article
Protein homology model refinement by large-scale energy optimization Open
Significance Protein structure refinement by direct global energy optimization has been a longstanding challenge in computational structural biology due to limitations in both energy function accuracy and conformational sampling. This manu…
View article
Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites Open
Evolutionary-rate variation among sites within proteins depends on functional and biophysical properties that constrain protein evolution. It is generally accepted that proteins must be able to fold stably in order to function. However, th…
View article
Properties of protein unfolded states suggest broad selection for expanded conformational ensembles Open
Significance Amino acid sequences are known to be crucial for specifying the folded structure of a protein. Here we show that sequences also play an important role in specifying the properties of a protein’s unfolded ensemble. For an autot…
View article
Selection on protein structure, interaction, and sequence Open
Characterizing the probabilities of observing amino acid substitutions at specific sites in a protein over evolutionary time is a major goal in the field of molecular evolution. While purely statistical approaches at different levels of co…
View article
Evolution, folding, and design of TIM barrels and related proteins Open
Proteins are chief actors in life that perform a myriad of exquisite functions. This diversity has been enabled through the evolution and diversification of protein folds. Analysis of sequences and structures strongly suggest that numerous…
View article
Evolution of Protein Domain Repeats in Metazoa Open
Repeats are ubiquitous elements of proteins and they play important roles for cellular function and during evolution. Repeats are, however, also notoriously difficult to capture computationally and large scale studies so far had difficulti…
View article
Thermophilic Proteins as Versatile Scaffolds for Protein Engineering Open
Literature from the past two decades has outlined the existence of a trade-off between protein stability and function. This trade-off creates a unique challenge for protein engineers who seek to introduce new functionality to proteins. The…
View article
An ambiguity principle for assigning protein structural domains Open
Our novel algorithm for delimiting protein structural domains provides insights into protein folding, function, and evolution.
View article
Dynamics-Evolution Correspondence in Protein Structures Open
The genotype-phenotype mapping of proteins is a fundamental question in structural biology. In this Letter, with the analysis of a large dataset of proteins from hundreds of protein families, we quantitatively demonstrate the correlations …
View article
Evolutionary trend toward kinetic stability in the folding trajectory of RNases H Open
Significance Because protein folding is crucial to proper cellular function, there must be evolutionary pressures on how a protein achieves and maintains its folded structure. The outcome of these pressures on a folding pathway should be r…
View article
Identification and Analysis of Natural Building Blocks for Evolution-Guided Fragment-Based Protein Design Open
Natural evolution has generated an impressively diverse protein universe via duplication and recombination from a set of protein fragments that served as building blocks. The application of these concepts to the design of new proteins usin…
View article
ProtASR: An Evolutionary Framework for Ancestral Protein Reconstruction with Selection on Folding Stability Open
The computational reconstruction of ancestral proteins provides information on past biological events and has practical implications for biomedicine and biotechnology. Currently available tools for ancestral sequence reconstruction (ASR) a…
View article
Patterns of coevolving amino acids unveil structural and dynamical domains Open
Significance Patterns of pairwise correlations in sequence alignments can be used to reconstruct the network of residue-residue contacts and thus the three-dimensional structure of proteins. Less explored, and yet extremely intriguing, is …
View article
Changing preferences: deformation of single position amino acid fitness landscapes and evolution of proteins Open
The fitness landscape—the function that relates genotypes to fitness—and its role in directing evolution are a central object of evolutionary biology. However, its huge dimensionality precludes understanding of even the basic aspects of it…
View article
Understanding enzyme function evolution from a computational perspective Open
In this review, we will explore recent computational approaches to understand enzyme evolution from the perspective of protein structure, dynamics and promiscuity. We will present quantitative methods to measure the size of evolutionary st…
View article
Substitution scoring matrices for proteins ‐ An overview Open
Sequence analysis is the primary and simplest approach to discover structural, functional and evolutionary details of related proteins. All the alignment based approaches of sequence analysis make use of amino acid substitution matrices, a…