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The inverse Ising problem and its generalizations to Potts and continuous spin models have recently attracted much attention thanks to their successful applications in the statistical modeling of biological data. In the standard setting,…

Quantitative Methods · Quantitative Biology 2017-03-06 Pierre Barrat-Charlaix , Matteo Figliuzzi , Martin Weigt

Self-supervised neural language models with attention have recently been applied to biological sequence data, advancing structure, function and mutational effect prediction. Some protein language models, including MSA Transformer and…

Biomolecules · Quantitative Biology 2022-10-25 Umberto Lupo , Damiano Sgarbossa , Anne-Florence Bitbol

We apply a new approach to the reverse protein folding problem. Our method uses a minimization function in the design process which is different from the energy function used for folding. For a lattice model, we show that this new approach…

Condensed Matter · Physics 2009-10-28 J. M. Deutsch , Tanya Kurosky

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,…

Biomolecules · Quantitative Biology 2022-10-12 Ezequiel A. Galpern , Jacopo Marchi , Thierry Mora , Aleksandra M. Walczak , Diego U. Ferreiro

We consider a generic representation problem of internal coordinates (bond lengths, valence angles, and dihedral angles) and their transformation to 3-dimensional Cartesian coordinates of a biomolecule. We show that the…

Inverse protein folding -- the task of predicting a protein sequence from its backbone atom coordinates -- has surfaced as an important problem in the "top down", de novo design of proteins. Contemporary approaches have cast this problem as…

Proteins created by combinatorial methods in vitro are an important source of information for understanding sequence-structure-function relationships. Alignments of folded proteins from combinatorial libraries can be analyzed using methods…

Biomolecules · Quantitative Biology 2007-05-23 Jeffrey B. Endelman , Jesse D. Bloom , Christopher R. Otey , Marco Landwehr , Frances H. Arnold

Learning Ising or Potts models from data has become an important topic in statistical physics and computational biology, with applications to predictions of structural contacts in proteins and other areas of biological data analysis. The…

Biological Physics · Physics 2018-09-19 Chen-Yi Gao , Hai-Jun Zhou , Erik Aurell

We introduce a lattice model of protein conformations which is able to reproduce second structures of proteins (alpha--helices and beta--sheets). This model is based on the following two main ideas. First, we model backbone parts of amino…

Soft Condensed Matter · Physics 2012-08-01 S. Albeverio , S. V. Kozyrev

Pairwise models like the Ising model or the generalized Potts model have found many successful applications in fields like physics, biology, and economics. Closely connected is the problem of inverse statistical mechanics, where the goal is…

Disordered Systems and Neural Networks · Physics 2022-01-12 Christoph Feinauer , Carlo Lucibello

Here we present an approximate analytical theory for the relationship between a protein structure's contact matrix and the shape of its energy spectrum in amino acid sequence space. We demonstrate a dependence of the number of sequences of…

Soft Condensed Matter · Physics 2009-11-07 Jeremy L. England , Eugene I. Shakhnovich

Protein structure prediction often hinges on multiple sequence alignments (MSAs), which underperform on low-homology and orphan proteins. We introduce PLAME, a lightweight MSA design framework that leverages evolutionary embeddings from…

Machine Learning · Computer Science 2025-09-29 Hanqun Cao , Xinyi Zhou , Zijun Gao , Chenyu Wang , Xin Gao , Zhi Zhang , Cesar de la Fuente-Nunez , Chunbin Gu , Ge Liu , Pheng-Ann Heng

Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational…

Biomolecules · Quantitative Biology 2025-06-18 Advaith Maddipatla , Nadav Bojan Sellam , Meital Bojan , Sanketh Vedula , Paul Schanda , Ailie Marx , Alex M. Bronstein

Inferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology. Structures are not known for the vast majority of protein sequences, but structure is critical for…

Machine Learning · Computer Science 2019-10-17 Tristan Bepler , Bonnie Berger

We discuss a stochastic approach for reconstructing the native structures of proteins from the knowledge of the "effective connectivity", which is a one-dimensional structural profile constructed as a linear combination of the eigenvectors…

Biological Physics · Physics 2009-01-20 Katrin Wolff , Michele Vendruscolo , Markus Porto

In view of the important role helix-sheet transitions play in protein aggregation, we introduce a simple model to study secondary structural transitions of helix-coil-sheet systems using a Potts model starting with an effective Hamiltonian.…

Biological Physics · Physics 2011-11-09 John S. Schreck , Jian-Min Yuan

The inverse problem is studied in multi-body systems with nonlinear dynamics representing, e.g., phase-locked wave systems, standard multimode and random lasers. Using a general model for four-body interacting complex-valued variables we…

Disordered Systems and Neural Networks · Physics 2017-08-01 Alessia Marruzzo , Payal Tyagi , Fabrizio Antenucci , Andrea Pagnani , Luca Leuzzi

We consider the problem of inferring a graphical Potts model on a population of variables, with a non-uniform number of Potts colors (symbols) across variables. This inverse Potts problem generally involves the inference of a large number…

The inverse Potts problem to infer a Boltzmann distribution for homologous protein sequences from their single-site and pairwise amino acid frequencies recently attracts a great deal of attention in the studies of protein structure and…

Populations and Evolution · Quantitative Biology 2024-07-23 Sanzo Miyazawa

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…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter