相关论文: Position Dependent and Independent Evolutionary Mo…
Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…
Methods for alignment of protein sequences typically measure similarity by using substitution matrix with scores for all possible exchanges of one amino acid with another. Although widely used, the matrices derived from homologous sequence…
The observed correlations between pairs of homologous protein sequences are typically explained in terms of a Markovian dynamic of amino acid substitution. This model assumes that every location on the protein sequence has the same…
Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a…
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,…
Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…
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…
We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…
Residue-residue interactions that fold a protein into a unique three-dimensional structure and make it play a specific function impose structural and functional constraints on each residue site. Selective constraints on residue sites are…
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,…
Scientific studies in many areas of biology routinely employ evolutionary analyses based on the probabilistic inference of phylogenetic trees from molecular sequence data. Evolutionary processes that act at the molecular level are highly…
We compare an evolutionary chemical model with simple empirical models of the abundance and with static chemical models. We focus on the prediction of molecular line profiles that are commonly observed in low mass star forming cores. We…
The possibility of deriving the contact potentials between amino acids from their frequencies of occurence in proteins is discussed in evolutionary terms. This approach allows the use of traditional thermodynamics to describe such…
The amino acid sequences of proteins provide rich information for inferring distant phylogenetic relationships and for predicting protein functions. Estimating the rate matrix of residue substitutions from amino acid sequences is also…
Evolutionary accumulation models (EvAMs) are an emerging class of machine learning methods designed to infer the evolutionary pathways by which features are acquired. Applications include cancer evolution (accumulation of mutations),…
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…
Markov models of character substitution on phylogenies form the foundation of phylogenetic inference frameworks. Early models made the simplifying assumption that the substitution process is homogeneous over time and across sites in the…
This work demonstrates how a complete statistical model quantifying the evolution of pairs of aligned proteins can be constructed from a time-parameterised substitution matrix and a time-parameterised 3-state alignment machine. All…
We present and implement a distance-based clustering of amino acids within the framework of a statistically derived interaction matrix and show that the resulting groups faithfully reproduce, for well-designed sequences, thermodynamic…
Window profiles of amino acids in protein sequences are taken as a description of the amino acid environment. The relative entropy or Kullback-Leibler distance derived from profiles is used as a measure of dissimilarity for comparison of…