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The similarity in the three-dimensional structures of homologous proteins imposes strong constraints on their sequence variability. It has long been suggested that the resulting correlations among amino acid compositions at different…

Proteins have evolved to perform diverse cellular functions, from serving as reaction catalysts to coordinating cellular propagation and development. Frequently, proteins do not exert their full potential as monomers but rather undergo…

Biomolecules · Quantitative Biology 2019-10-07 Guido Uguzzoni , Shalini John Lovis , Francesco Oteri , Alexander Schug , Hendrik Szurmant , Martin Weigt

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…

Quantitative Methods · Quantitative Biology 2014-04-07 Carlo Baldassi , Marco Zamparo , Christoph Feinauer , Andrea Procaccini , Riccardo Zecchina , Martin Weigt , Andrea Pagnani

Understanding protein-protein interactions is central to our understanding of almost all complex biological processes. Computational tools exploiting rapidly growing genomic databases to characterize protein-protein interactions are…

Quantitative Methods · Quantitative Biology 2016-10-28 Thomas Gueudré , Carlo Baldassi , Marco Zamparo , Martin Weigt , Andrea Pagnani

Determining which proteins interact together is crucial to a systems-level understanding of the cell. Recently, algorithms based on Direct Coupling Analysis (DCA) pairwise maximum-entropy models have allowed to identify interaction partners…

Biomolecules · Quantitative Biology 2020-03-25 Guillaume Marmier , Martin Weigt , Anne-Florence Bitbol

Various approaches have explored the covariation of residues in multiple-sequence alignments of homologous proteins to extract functional and structural information. Among those are principal component analysis (PCA), which identifies the…

Biomolecules · Quantitative Biology 2013-08-28 Simona Cocco , Remi Monasson , Martin Weigt

The analysis of correlations of amino acid occurrences in globular proteins has led to the development of statistical tools that can identify native contacts -- portions of the chains that come to close distance in folded structural…

Biomolecules · Quantitative Biology 2014-07-28 Rocío Espada , R. Gonzalo Parra , Thierry Mora , Aleksandra M. Walczak , Diego Ferreiro

Direct-Coupling Analysis is a group of methods to harvest information about coevolving residues in a protein family by learning a generative model in an exponential family from data. In protein families of realistic size, this learning can…

Quantitative Methods · Quantitative Biology 2014-09-16 Magnus Ekeberg , Tuomo Hartonen , Erik Aurell

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…

Biomolecules · Quantitative Biology 2013-01-18 Sanzo Miyazawa

Many non-coding RNAs are known to play a role in the cell directly linked to their structure. Structure prediction based on the sole sequence is however a challenging task. On the other hand, thanks to the low cost of sequencing…

Quantitative Methods · Quantitative Biology 2020-05-05 Francesca Cuturello , Guido Tiana , Giovanni Bussi

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…

Biomolecules · Quantitative Biology 2019-09-25 Kai Shimagaki , Martin Weigt

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…

Quantitative Methods · Quantitative Biology 2013-01-15 Magnus Ekeberg , Cecilia Lövkvist , Yueheng Lan , Martin Weigt , Erik Aurell

Boltzmann machines (BM) are widely used as generative models. For example, pairwise Potts models (PM), which are instances of the BM class, provide accurate statistical models of families of evolutionarily related protein sequences. Their…

Biomolecules · Quantitative Biology 2021-08-09 Pierre Barrat-Charlaix , Anna Paola Muntoni , Kai Shimagaki , Martin Weigt , Francesco Zamponi

Inferring protein-protein interactions from sequences is an important task in computational biology. Recent methods based on Direct Coupling Analysis (DCA) or Mutual Information (MI) allow to find interaction partners among paralogs of two…

Biomolecules · Quantitative Biology 2022-05-19 Andonis Gerardos , Nicola Dietler , Anne-Florence Bitbol

Motivation: Standard algorithms for pairwise protein sequence alignment make the simplifying assumption that amino acid substitutions at neighboring sites are uncorrelated. This assumption allows implementation of fast algorithms for…

Biomolecules · Quantitative Biology 2014-05-27 Gavin E. Crooks , Richard E. Green , Steven E. Brenner

Sequences of nucleotides (for DNA and RNA) or amino acids (for proteins) are central objects in biology. Among the most important computational problems is that of sequence alignment, i.e. arranging sequences from different organisms in…

Quantitative Methods · Quantitative Biology 2020-12-08 Anna Paola Muntoni , Andrea Pagnani , Martin Weigt , Francesco Zamponi

Identifying protein-protein interactions is crucial for a systems-level understanding of the cell. Recently, algorithms based on inverse statistical physics, e.g. Direct Coupling Analysis (DCA), have allowed to use evolutionarily related…

Biomolecules · Quantitative Biology 2020-03-25 Carlos A. Gandarilla-Pérez , Pierre Mergny , Martin Weigt , Anne-Florence Bitbol

Direct Coupling Analysis (DCA) is a now widely used method to leverage statistical information from many similar biological systems to draw meaningful conclusions on each system separately. DCA has been applied with great success to…

Populations and Evolution · Quantitative Biology 2018-08-13 Chen-Yi Gao , Fabio Cecconi , Angelo Vulpiani , Hai-Jun Zhou , Erik Aurell

The evolutionary trajectory of a protein through sequence space is constrained by function and three-dimensional (3D) structure. Residues in spatial proximity tend to co-evolve, yet attempts to invert the evolutionary record to identify…

Biomolecules · Quantitative Biology 2015-03-13 Debora S. Marks , Lucy J. Colwell , Robert Sheridan , Thomas A. Hopf , Andrea Pagnani , Riccardo Zecchina , Chris Sander

Protein-protein interactions are fundamental to many biological processes. Experimental screens have identified tens of thousands of interactions and structural biology has provided detailed functional insight for select 3D protein…

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