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Predicting three dimensional residue-residue contacts from evolutionary information in protein sequences was attempted already in the early 1990s. However, contact prediction accuracies of methods evaluated in CASP experiments before CASP11…

Biomolecules · Quantitative Biology 2018-10-16 Sanzo Miyazawa

Function of proteins or a network of interacting proteins often involves communication between residues that are well separated in sequence. The classic example is the participation of distant residues in allosteric regulation.…

Biomolecules · Quantitative Biology 2007-05-23 Ruxandra I. Dima , D. Thirumalai

The functions of proteins and RNAs are determined by a myriad of interactions between their constituent residues, but most quantitative models of how molecular phenotype depends on genotype must approximate this by simple additive effects.…

Quantitative Methods · Quantitative Biology 2017-12-19 Adam J. Riesselman , John B. Ingraham , Debora S. Marks

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

Understanding protein sequences is vital and urgent for biology, healthcare, and medicine. Labeling approaches are expensive yet time-consuming, while the amount of unlabeled data is increasing quite faster than that of the labeled data due…

Computation and Language · Computer Science 2021-11-01 Liang He , Shizhuo Zhang , Lijun Wu , Huanhuan Xia , Fusong Ju , He Zhang , Siyuan Liu , Yingce Xia , Jianwei Zhu , Pan Deng , Bin Shao , Tao Qin , Tie-Yan Liu

It is acknowledged that co-evolutionary nucleotide-nucleotide interactions are essential for RNA structures and functions. Currently, direct coupling analysis (DCA) infers nucleotide contacts in a sequence from its homologous sequence…

Biomolecules · Quantitative Biology 2017-11-30 Yiren Jian , Chen Zeng , Yunjie Zhao

To construct models of large, multivariate complex systems, such as those in biology, one needs to constrain which variables are allowed to interact. This can be viewed as detecting "local" structures among the variables. In the context of…

Data Analysis, Statistics and Probability · Physics 2023-10-19 Mahajabin Rahman , Ilya Nemenman

Protein contacts contain important information for protein structure and functional study, but contact prediction from sequence remains very challenging. Both evolutionary coupling (EC) analysis and supervised machine learning methods are…

Quantitative Methods · Quantitative Biology 2015-04-09 Jianzhu Ma , Sheng Wang , Zhiyong Wang , Jinbo Xu

Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…

Quantitative Methods · Quantitative Biology 2024-11-04 Liang He , Peiran Jin , Yaosen Min , Shufang Xie , Lijun Wu , Tao Qin , Xiaozhuan Liang , Kaiyuan Gao , Yuliang Jiang , Tie-Yan Liu

Multiple sequence alignment (MSA) data play a crucial role in the study of protein mutations, with contact prediction being a notable application. Existing methods are often model-based or algorithmic and typically do not incorporate…

Methodology · Statistics 2026-01-23 Fan Yang , Zhao Ren , Wen Zhou , Kejue Jia , Robert Jernigan

Two recent streams of work suggest that pairwise interactions may be sufficient to capture the complexity of biological systems ranging from protein structure to networks of neurons. In one approach, possible amino acid sequences in a…

Quantitative Methods · Quantitative Biology 2007-12-31 William Bialek , Rama Ranganathan

Recently, persistent homology has had tremendous success in biomolecular data analysis. It works by examining the topological relationship or connectivity of a group of atoms in a molecule at a variety of scales, then rendering a family of…

Biomolecules · Quantitative Biology 2019-03-27 David Bramer , Guo-Wei Wei

Predicting protein structure from the amino acid sequence has been a challenge with theoretical and practical significance in biophysics. Despite the recent progresses elicited by improved residue-residue contact prediction, contact-based…

Biomolecules · Quantitative Biology 2019-12-19 Wenze Ding , Haipeng Gong

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.…

Biomolecules · Quantitative Biology 2017-01-18 Thomas A. Hopf , John B. Ingraham , Frank J. Poelwijk , Michael Springer , Chris Sander , Debora S. Marks

Studying evolutionary correlations in alignments of homologous sequences by means of an inverse Potts model has proven useful to obtain residue-residue contact energies and to predict contacts in proteins. The quality of the results depend…

Biomolecules · Quantitative Biology 2019-09-04 G. Franco , M. Cagiada , G. Bussi , G. Tiana

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,…

Biomolecules · Quantitative Biology 2019-10-07 Simona Cocco , Christoph Feinauer , Matteo Figliuzzi , Remi Monasson , Martin Weigt

We predict analytically that diagonal correlations of amino acid positions within protein sequences statistically enhance protein propensity for nonspecific binding. We use the term 'promiscuity' to describe such nonspecific binding.…

Biomolecules · Quantitative Biology 2011-08-16 David B. Lukatsky , Ariel Afek , Eugene I. Shakhnovich

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…

Methodology · Statistics 2025-05-22 Bingying Dai , Yinan Lin , Kejue Jia , Zhao Ren , Wen Zhou

Statistical coupling analysis (SCA) is a method for analyzing multiple sequence alignments that was used to identify groups of coevolving residues termed "sectors". The method applies spectral analysis to a matrix obtained by combining…

Biomolecules · Quantitative Biology 2015-06-19 Tiberiu Tesileanu , Lucy J. Colwell , Stanislas Leibler

The multiple sequence alignment (MSA) of a protein family provides a wealth of information in terms of the conservation pattern of amino acid residues not only at each alignment site but also between distant sites. In order to statistically…

Biomolecules · Quantitative Biology 2016-04-27 Akira R. Kinjo