Related papers: Revealing evolutionary constraints on proteins thr…
Statistical analysis of multiple sequence alignments of homologous proteins has revealed groups of coevolving amino acids called sectors. These groups of amino-acid sites feature collective correlations in their amino-acid usage, and they…
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…
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…
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…
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…
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…
The sequence of amino acids in a protein is believed to determine its native state structure, which in turn is related to the functionality of the protein. In addition, information pertaining to evolutionary relationships is contained in…
Studies of coevolution of amino acids within and between proteins have revealed two types of coevolving units: coevolving contacts, which are pairs of amino acids distant along the sequence but in contact in the three-dimensional structure,…
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.…
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…
The discovery of motifs underlying gene expression is a challenging one. Some of these motifs are known transcription factors, but sequence inspection often provides valuable clues, even discovery of novel motifs with uncharacterized…
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…
The function of proteins arises from cooperative interactions and rearrangements of their amino acids, which exhibit large-scale dynamical modes. Long-range correlations have also been revealed in protein sequences, and this has motivated…
How DNA is mapped to functional proteins is a basic question of living matter. We introduce and study a physical model of protein evolution which suggests a mechanical basis for this map. Many proteins rely on large-scale motion to…
During their evolution, proteins explore sequence space via an interplay between random mutations and phenotypic selection. Here we build upon recent progress in reconstructing data-driven fitness landscapes for families of homologous…
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…
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…
The proper biological functioning of proteins often relies on the occurrence of coordinated fluctuations around their native structure, or of wider and sometimes highly elaborated motions. Coarse-grained elastic-network descriptions are…
Composed of amino acid chains that influence how they fold and thus dictating their function and features, proteins are a class of macromolecules that play a central role in major biological processes and are required for the structure,…
We show how to localize and quantify the functional evolutionary constraints on natural proteins. The method compares the perturbations caused by local sequence variants to the energetics of the protein folding process and to the…