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Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution…

Populations and Evolution · Quantitative Biology 2015-06-12 Armita Nourmohammad , Stephan Schiffels , Michael Laessig

In this work, we discovered a fundamental connection between selection for protein stability and emergence of preferred structures of proteins. Using standard exact 3-dimensional lattice model we evolve sequences starting from random ones…

Genomics · Quantitative Biology 2007-05-23 Konstantin B. Zeldovich , Igor N. Berezovsky , Eugene I. Sha

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

It has recently been discovered that many biological systems, when represented as graphs, exhibit a scale-free topology. One such system is the set of structural relationships among protein domains. The scale-free nature of this and other…

Populations and Evolution · Quantitative Biology 2009-11-10 Eric J. Deeds , Eugene I. Shakhnovich

In this work we propose a physical model of organismal evolution, where phenotype, organism life expectancy, is directly related to genotype i.e. the stability of its proteins which can be determined exactly in the model. Simulating the…

Populations and Evolution · Quantitative Biology 2007-05-23 Konstantin B. Zeldovich , Boris E. Shakhnovich , Eugene I. Shakhnovich

Evolutionary dynamics is often viewed as a subtle process of change accumulation that causes a divergence among organisms and their genomes. However, this interpretation is an inheritance of a gradualistic view that has been challenged at…

Populations and Evolution · Quantitative Biology 2018-07-27 Jacobo Aguirre , Pablo Catalán , José A. Cuesta , Susanna Manrubia

Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…

Biomolecules · Quantitative Biology 2025-05-26 Ezequiel A. Galpern , Federico Caamaño , Diego U. Ferreiro

Evolving biomolecular networks have to combine the stability against perturbations with flexibility allowing their constituents to assume new roles in the cell. Gene duplication followed by functional divergence of associated proteins is a…

Molecular Networks · Quantitative Biology 2007-05-23 Sergei Maslov , Kim Sneppen , Kasper Astrup Eriksen

How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…

Biomolecules · Quantitative Biology 2025-11-04 Carlos Bustamante , Christian Kaiser , Erik Lindahl , Robert Sosa , Giovanni Volpe

Current-day genomes bear the mark of the evolutionary processes. One of the strongest indications is the sequence homology among families of proteins that perform similar biological functions in different species. The number of proteins in…

Biological Physics · Physics 2007-05-23 Joel S. Bader

Protein structures in nature often exhibit a high degree of regularity (secondary structures, tertiary symmetries, etc.) absent in random compact conformations. We demonstrate in a simple lattice model of protein folding that structural…

Condensed Matter · Physics 2009-10-28 Hao Li , Robert Helling , Chao Tang , Ned Wingreen

Biological diversity has evolved despite the essentially infinite complexity of protein sequence space. We present a hierarchical approach to the efficient searching of this space and quantify the evolutionary potential of our approach with…

Statistical Mechanics · Physics 2009-10-31 Leonard D. Bogarad , Michael W. Deem

Most of the DNA that composes a complex organism is non-coding and defined as junk. Even the coding part is composed of genes that affect the phenotype differently. Therefore, a random mutation has an effect on the specimen fitness that…

Populations and Evolution · Quantitative Biology 2021-07-19 Mattia Miotto , Lorenzo Monacelli

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…

Populations and Evolution · Quantitative Biology 2020-09-22 Michael Golden , Eduardo García-Portugués , Michael Sørensen , Kanti V. Mardia , Thomas Hamelryck , Jotun Hein

The study of genomic variation has provided key insights into the functional role of mutations. Predominantly, studies have focused on single nucleotide variants (SNV), which are relatively easy to detect and can be described with rich…

Genomics · Quantitative Biology 2015-09-04 Daniel R. Zerbino , Tracy Ballinger , Benedict Paten , Glenn Hickey , David Haussler

We present an analysis of the effects of global topology on the structural stability of folded proteins in thermal equilibrium with a heat bath. For a large class of single domain proteins, we computed the harmonic spectrum within the…

Biomolecules · Quantitative Biology 2007-05-23 R. Burioni , D. Cassi , F. Cecconi , A. Vulpiani

A representation of the genetic code as a six-dimensional Boolean hypercube is proposed. It is assumed here that this structure is the result of the hierarchical order of the interaction energies of the bases in codon-anticodon recognition.…

Soft Condensed Matter · Physics 2007-05-23 Miguel A. Jimenez-Montano , Carlos R. de la Mora-Basanez , Thorsten Poeschel

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg

We present an analysis of the role of global topology on the structural stability of folded proteins in thermal equilibrium with a heat bath. For a large class of single domain proteins, we compute the harmonic spectrum within the Gaussian…

Condensed Matter · Physics 2007-05-23 R. Burioni , D. Cassi , F. Cecconi , A. Vulpiani

The prediction of the three-dimensional native structure of proteins from the knowledge of their amino acid sequence, known as the protein folding problem, is one of the most important yet unsolved issues of modern science. Since the…

Biological Physics · Physics 2008-11-24 Pablo Echenique