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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

We introduce a formulation for normal mode analyses of globular proteins that significantly improves on an earlier, 1-parameter formulation (M. Tirion, PRL 77, 1905 (1996)) that characterized the slow modes associated with protein data bank…

Biological Physics · Physics 2015-04-01 Monique M. Tirion , Daniel ben-Avraham

In many models of genotypic evolution, the vector of genotype populations satisfies a system of linear ordinary differential equations. This system of equations models a competition between differential replication rates (fitness) and…

Populations and Evolution · Quantitative Biology 2009-11-13 Charles L. Epstein

The native state structures of globular proteins are stable and well-packed indicating that self-interactions are favored over protein-solvent interactions under folding conditions. We use this as a guiding principle to derive the geometry…

Biomolecules · Quantitative Biology 2021-07-14 Tatjana Škrbić , Amos Maritan , Achille Giacometti , George D. Rose , Jayanth R. Banavar

Identifying and characterizing mutational paths is an important issue in evolutionary biology and in bioengineering. We here introduce a generic description of mutational paths in terms of the goodness of sequences and of the mutational…

Biomolecules · Quantitative Biology 2023-03-29 Eugenio Mauri , Simona Cocco , Rémi Monasson

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…

Machine Learning · Computer Science 2025-01-31 Karishma Thakrar , Jiangqin Ma , Max Diamond , Akash Patel

Predicting protein stability changes induced by single-point mutations has been a persistent challenge over the years, attracting immense interest from numerous researchers. The ability to precisely predict protein thermostability is…

Biomolecules · Quantitative Biology 2023-12-08 Yijie Zhang , Zhangyang Gao , Cheng Tan , Stan Z. Li

We propose a class of evolutionary models that involves an arbitrary exchangeable process as the breeding process and different selection schemes. In those models, a new genome is born according to the breeding process, and then a genome is…

Neural and Evolutionary Computing · Computer Science 2020-08-25 Jüri Lember , Chris Watkins

In this work we employ various methods of analysis (unfolding simulations and comparative analysis of structures and sequences of proteomes of thermophilic organisms) to show that organisms can follow two major strategies of thermophilic…

Biomolecules · Quantitative Biology 2007-05-23 Igor N. Berezovsky , Eugene I. Shakhnovich

A central challenge in the study of protein evolution is the identification of historic amino acid sequence changes responsible for creating novel functions observed in present-day proteins. To address this problem, we developed a new…

Genomics · Quantitative Biology 2014-06-13 Victor Hanson-Smith , Christopher Baker , Alexander Johnson

A simple lattice model for proteins that allows for distinct sizes of the amino acids is presented. The model is found to lead to a significant number of conformations that are the unique ground state of one or more sequences or encodable.…

Statistical Mechanics · Physics 2009-10-30 Cristian Micheletti , Jayanth R. Banavar , Amos Maritan , Flavio Seno

Phase separation has emerged as an essential concept for the spatial organization inside biological cells. However, despite the clear relevance to virtually all physiological functions, we understand surprisingly little about what phases…

Biological Physics · Physics 2022-08-10 David Zwicker , Liedewij Laan

Normal mode analysis is a widely used technique for reconstructing conformational changes of proteins from the knowledge of native structures. In this Letter, we investigate to what extent normal modes capture the salient features of the…

Statistical Mechanics · Physics 2015-05-13 Francesco Piazza , Paolo De Los Rios , Fabio Cecconi

The majority of mammalian genomic transcripts do not directly code for proteins and it is currently believed that most of these are not under evolutionary constraint. However given the abundance non-coding RNA (ncRNA) and its strong…

Molecular Networks · Quantitative Biology 2016-08-22 J. M. Deutsch

Biological systems, with many interacting components, face high-dimensional environmental fluctuations, ranging from diverse nutrient deprivations to toxins, drugs, and physical stresses. Yet, many biological control mechanisms are `simple'…

Biological Physics · Physics 2025-07-17 Christopher Joel Russo , Kabir Husain , Rama Ranganathan , David Pincus , Arvind Murugan

In this Communication we present statistical analysis of conservation profiles in families of homologous sequences for nine proteins whose folding nucleus was determined by protein engineering methods. We show that in all but one protein…

Biological Physics · Physics 2007-05-23 Leonid Mirny , Eugene Shakhnovich

Many of the concepts which are at the basis of the development associated with a quantitative treatment of the variety of phenomena associated with the spontaneous breaking of gauge symmetry in nuclei have been instrumental in connection…

Nuclear Theory · Physics 2017-08-23 R. A. Broglia

The ratio of non-synonymous to synonymous substitutions $\omega(=d_{N}/d_{S})$ has been widely used as a measure of adaptive evolution in protein coding genes. Omega can be defined in terms of population genetics parameters as the fixation…

Populations and Evolution · Quantitative Biology 2013-11-27 Mario dos Reis

Nuclear magnetic relaxation is widely used to probe protein dynamics. For decades, most analyses of relaxation in proteins have relied successfully on the model-free approach, forgoing mechanistic descriptions of motions. Model-free types…

A fundamental question for evolutionary biology is why rates of evolution vary dramatically between proteins. Perhaps surprisingly, it is controversial how much a protein's functional importance affects its rate of evolution. In most…

Populations and Evolution · Quantitative Biology 2009-09-20 Ryan N. Gutenkunst
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