Related papers: Quantification of the effect of mutations using a …
Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…
Quantifying the effects of amino acid mutations in proteins presents a significant challenge due to the vast combinations of residue sites and amino acid types, making experimental approaches costly and time-consuming. The Potts model has…
Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…
We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…
Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish…
In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques,…
The ability to absorb mutations while retaining structure and function, or mutational robustness, is a remarkable property of natural proteins. In this Letter, we use a computational model of organismic evolution [Zeldovich et al, PLOS Comp…
Many crucial biological processes rely on networks of protein-protein interactions. Predicting the effect of amino acid mutations on protein-protein binding is vital in protein engineering and therapeutic discovery. However, the scarcity of…
In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our…
Identifying and characterizing mutational paths is an important issue in evolutionary biology and in bioengineering. We here introduce a generic description of mutational paths in terms of the goodness of sequences and of the mutational…
The fitness contribution of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations under selection, and can shape the…
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
Directed evolution plays an indispensable role in protein engineering that revises existing protein sequences to attain new or enhanced functions. Accurately predicting the effects of protein variants necessitates an in-depth understanding…
Evolution has fascinated quantitative and physical scientists for decades: how can the random process of mutation, recombination, and duplication of genetic information generate the diversity of life? What determines the rate of evolution?…
Empirical substitution matrices represent the average tendencies of substitutions over various protein families by sacrificing gene-level resolution. We develop a codon-based model, in which mutational tendencies of codon, a genetic code,…
Mutations are typically classified by their effects on the nucleotide sequence and by their size. Here, we argue that if our main aim is to understand the effect of mutations on evolutionary outcomes (such as adaptation or speciation), we…
We are interested in modelling Darwinian evolution, resulting from the interplay of phenotypic variation and natural selection through ecological interactions. Our models are rooted in the microscopic, stochastic description of a population…
Predicting the stability and fitness effects of amino acid mutations in proteins is a cornerstone of biological discovery and engineering. Various experimental techniques have been developed to measure mutational effects, providing us with…
Motivation: Site directed mutagenesis is widely used to understand the structure and function of biomolecules. Computational prediction of protein mutation impacts offers a fast, economical and potentially accurate alternative to laboratory…
Evolution is a dynamic process. The two classical forces of evolution are mutation and selection. Assuming small mutation rates, evolution can be predicted based solely on the fitness differences between phenotypes. Predicting an…