Related papers: Protein Structure and Evolutionary History Determi…
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,…
Understanding the protein folding process is an outstanding issue in biophysics; recent developments in molecular dynamics simulation have provided insights into this phenomenon. However, the large freedom of atomic motion hinders the…
Proteins are a matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with multifarious biochemistry. But it is also an instantiation along an evolutionary trajectory determined by the function…
Biologists have long sought a way to explain how statistical properties of genetic sequences emerged and are maintained through evolution. On the one hand, non-random structures at different scales indicate a complex genome organisation. On…
Eukaryote genomes contain excessively introns, inter-genic and other non-genic sequences that appear to have no vital functional role or phenotype manifestation. Their existence, a long-standing puzzle, is viewed from the principle of…
We present a statistical mechanics approach to the protein folding problem. We first review some of the basic properties of proteins, and introduce some physical models to describe their thermodynamics. These models rely on a random…
We argue that protein native state structures reside in a novel "phase" of matter which confers on proteins their many amazing characteristics. This phase arises from the common features of all globular proteins and is characterized by a…
Genetic sequences are known to possess non-trivial composition together with symmetries in the frequencies of their components. Recently, it has been shown that symmetry and structure are hierarchically intertwined in DNA, suggesting a…
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…
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…
Topology affects physical and biological properties of DNA and impacts fundamental cellular processes, such as gene expression, genome replication, chromosome structure and segregation. In all organisms DNA topology is carefully modulated…
Spatial transcriptomics studies are becoming increasingly large and commonplace, necessitating simultaneous analysis of a large number of spatially resolved variables. Correspondingly, a diverse range of methodologies have been proposed 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…
Novel numerical techniques, validated by an analysis of barnase and chymotrypsin inhibitor, are used to elucidate the paramount role played by the geometry of the protein backbone in steering the folding to the correct native state. It is…
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…
An essential quantity to ensure evolvability of populations is the navigability of the genotype space. Navigability relies on the existence of sufficiently large genotype networks, that is ensembles of sequences with the same phenotype that…
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…
Only about 1,000 qualitatively different protein folds are believed to exist in nature. Here, we review theoretical studies which suggest that some folds are intrinsically more designable than others, {\it i.e.} are lowest energy states of…
Heterozygote disadvantage is potentially a potent driver of population genetic divergence. Also referred to as underdominance, this phenomena describes a situation where a genetic heterozygote has a lower overall fitness than either…
What are the structural determinants of protein sequence evolution? A number of site-specific structural characteristics have been proposed, most of which are broadly related to either the density of contacts or the solvent accessibility of…