Related papers: Inferring repeat protein energetics from evolution…
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…
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,…
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…
A general theoretical framework is developed using free energy functional methods to understand the effects of heterogeneity in the folding of a well-designed protein. Native energetic heterogeneity arising from non-uniformity in native…
Some natural proteins display recurrent structural patterns. Despite being highly similar at the tertiary structure level, repetitions within a single repeat protein can be extremely variable at the sequence level. We propose a mathematical…
We use a free energy functional theory to elucidate general properties of heterogeneously ordering, fast folding proteins, and we test our conclusions with lattice simulations. We find that both structural and energetic heterogeneity can…
In the protein sequence space, natural proteins form clusters of families which are characterized by their unique native folds whereas the great majority of random polypeptides are neither clustered nor foldable to unique structures. Since…
Though the problem of sequence-reversed protein folding is largely unexplored, one might speculate that reversed native protein sequences should be significantly more foldable than purely random heteropolymer sequences. In this article, we…
We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…
The primary structure of proteins, that is their sequence, represents one of the most abundant set of experimental data concerning biomolecules. The study of correlations in families of co--evolving proteins by means of an inverse…
The notion of energy landscapes provides conceptual tools for understanding the complexities of protein folding and function. Energy Landscape Theory indicates that it is much easier to find sequences that satisfy the "Principle of Minimal…
Natural proteins fold to a unique, thermodynamically dominant state. Modeling of the folding process and prediction of the native fold of proteins are two major unsolved problems in biophysics. Here, we show successful all-atom ab initio…
The analysis of correlations of amino acid occurrences in globular proteins has led to the development of statistical tools that can identify native contacts -- portions of the chains that come to close distance in folded structural…
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,…
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…
Protein evolution involves mutations occurring across a wide range of time scales. In analogy with disordered systems in statistical physics, this dynamical heterogeneity suggests strong correlations between mutations happening at distinct…
Making use of a simplified model for protein folding, it can be shown that conformations which are particularly stable when their energy is minimized with respect to amino acid sequence (in the sense that they display a large energy gap to…
The number of protein structures is far less than the number of sequences. By imposing simple generic features of proteins (low energy and compaction) on all possible sequences we show that the structure space is sparse compared to the…
Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence…
We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…