相关论文: Modeling and prediction of mutation fitness on pro…
Potts statistical models have become a popular and promising way to analyze mutational covariation in protein Multiple Sequence Alignments (MSAs) in order to understand protein structure, function and fitness. But the statistical…
Statistical models for families of evolutionary related proteins have recently gained interest: in particular pairwise Potts models, as those inferred by the Direct-Coupling Analysis, have been able to extract information about the…
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.…
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…
Recent generative learning models applied to protein multiple sequence alignment (MSA) datasets include simple and interpretable physics-based Potts covariation models and other machine learning models such as MSA-Transformer (MSA-T). The…
Understanding how protein mutations affect protein structure is essential for advancements in computational biology and bioinformatics. We introduce PRIMRose, a novel approach that predicts energy values for each residue given a mutated…
Spatially proximate amino acids in a protein tend to coevolve. A protein's three-dimensional (3D) structure hence leaves an echo of correlations in the evolutionary record. Reverse engineering 3D structures from such correlations is an open…
Correlation patterns in multiple sequence alignments of homologous proteins can be exploited to infer information on the three-dimensional structure of their members. The typical pipeline to address this task, which we in this paper refer…
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,…
Inverse statistical approaches to determine protein structure and function from Multiple Sequence Alignments (MSA) are emerging as powerful tools in computational biology. However the underlying assumptions of the relationship between the…
Predicting the impact of single-point amino acid mutations on protein stability is essential for understanding disease mechanisms and advancing drug development. Protein stability, quantified by changes in Gibbs free energy ($\Delta\Delta…
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…
A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…
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…
Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. Due to their symmetry, these proteins constitute excellent model systems to investigate how evolution relates to structure,…
The interaction between proteins and nucleic acids is crucial for processes that sustain cellular function, including DNA maintenance and the regulation of gene expression and translation. Amino acid mutations in protein-nucleic acid…
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…
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…
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…
The simplest approximation of interaction potential between amino-acids in proteins is the contact potential, which defines the effective free energy of a protein conformation by a set of amino acid contacts formed in this conformation.…