Related papers: Understanding hierarchical protein evolution from …
It has been conjectured that evolution exerted pressure to preserve amino acids bearing thermodynamic, kinetic, and functional roles. In this letter we show that the physical requirement to maintain protein stability gives rise to a…
In this work we develop a microscopic physical model of early evolution, where phenotype,organism life expectancy, is directly related to genotype, the stability of its proteins in their native conformations which can be determined exactly…
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…
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…
Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
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,…
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…
We propose a protein model based on a hierarchy of constraints that force the protein to follow certain pathways when changing conformation. The model exhibits a first order phase transition, cooperativity and is exactly solvable. It also…
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…
One of the most puzzling and unsolved challenges in molecular biology is understanding how proteins fold. Despite having advanced predictive tools that can accurately estimate the native structures of proteins, we still lack a comprehensive…
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…
Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability…
The protein folding problem must ultimately be solved on all length scales from the atomic up through a hierarchy of complicated structures. By analyzing the stability of the folding process using physics and mathematics, this paper shows…
Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…
Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…
Emergence of new protein structures has proved difficult to trace in nature and engineer in the laboratory. However, one aspect of structure evolution has proved immensely helpful for determining the three-dimensional structure of proteins…
Protein structures are much more conserved than sequences during evolution. Based on this observation, we investigate the consequences of structural conservation on protein evolution. We study seven of the most studied protein folds,…
The coding space of protein sequences is shaped by evolutionary constraints set by requirements of function and stability. We show that the coding space of a given protein family--the total number of sequences in that family--can be…
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…