Related papers: Proteins Evolution Upon Point Mutations
Natural protein sequences that self-assemble to form globular structures are compact with high packing densities in the folded states. It is known that proteins unfold upon addition of denaturants, adopting random coil structures. The…
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…
The mutation and selection of regulatory DNA sequences is presented as an ideal model system of molecular evolution where genotype, phenotype, and fitness can be explicitly and independently characterized. In this theoretical study, we…
We propose a minimal model to simulate long waiting times followed by evolutionary bursts on rugged landscapes. It combines point and inversions-like mutations as sources of genetic variation. The inversions are intended to simulate one of…
Recent single-molecule force measurements on single-domain proteins have highlighted a three-state folding mechanism where a stabilized intermediate state (I) is observed on the folding trajectory between the stretched state and the native…
Fitness effects of mutations fall on a continuum ranging from lethal to deleterious to beneficial. The distribution of fitness effects (DFE) among random mutations is an essential component of every evolutionary model and a mathematical…
Cells often exhibit different and stable phenotypes from the same DNA sequence. Robustness and plasticity of such cellular states are controlled by diverse transcriptional and epigenetic mechanisms, among them the modification of…
Biological forces govern essential cellular and molecular processes in all living organisms. Many cellular forces, e.g. those generated in cyclic conformational changes of biological machines, have repetitive components. However, little is…
Mutations are typically classified by their effects on the nucleotide sequence and by their size. Here, we argue that if our main aim is to understand the effect of mutations on evolutionary outcomes (such as adaptation or speciation), we…
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…
The role of the selection pressure and mutation amplitude on the behavior of a single-species population evolving on a two-dimensional lattice, in a periodically changing environment, is studied both analytically and numerically. The…
We consider classically scale-invariant theories with non-minimally coupled scalar fields, where the Planck mass and the hierarchy of physical scales are dynamically generated. The classical theories possess a fixed point, where scale…
This paper concerns piecewise-smooth maps on $\mathbb{R}^d$ that are continuous but not differentiable on switching manifolds (where the functional form of the map changes). The stability of fixed points on switching manifolds is…
It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate…
A mutator is an allele that increases the mutation rate throughout the genome by disrupting some aspect of DNA replication or repair. Mutators that increase the mutation rate by the order of 100 fold have been observed to spontaneously…
Epistasis occurs when the effect of a mutation depends on its carrier's genetic background. Despite increasing evidence that epistasis for fitness is common, its role during evolution is contentious. Fitness landscapes, mappings of genotype…
Astronomical observations have a unique ability to determine the laws of physics at distant times in the universe. They, therefore, have particular relevance in answering the basic question as to whether the laws of physics are invariant…
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…
Inverse folding models have proven to be highly effective zero-shot predictors of protein stability. Despite this success, the link between the amino acid preferences of an inverse folding model and the free-energy considerations underlying…
We introduce a data-driven epistatic model of protein evolution, capable of generating evolutionary trajectories spanning very different time scales reaching from individual mutations to diverged homologs. Our in silico evolution…