Related papers: Are residues in a protein folding nucleus evolutio…
Binding interactions between proteins and other molecules mediate numerous cellular processes, including metabolism, signaling, and regulation of gene expression. These interactions evolve in response to changes in the protein's chemical or…
Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…
Under certain conditions, the dynamics of coarse-grained models of solvated proteins can be described using a Markov state model, which tracks the evolution of populations of configurations. The transition rates among states that appear in…
In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with…
The ratio of non-synonymous to synonymous substitutions $\omega(=d_{N}/d_{S})$ has been widely used as a measure of adaptive evolution in protein coding genes. Omega can be defined in terms of population genetics parameters as the fixation…
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…
We apply a simulational proxy of the phi-value analysis and perform extensive mutagenesis experiments to identify the nucleating residues in the folding reactions of two small lattice Go polymers with different native geometries. These…
Many native structures of proteins accomodate complex topological motifs such as knots, lassos, and other geometrical entanglements. How proteins can fold quickly even in the presence of such topological obstacles is a debated question in…
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…
Predicting protein properties is paramount for biological and medical advancements. Current protein engineering mutates on a typical protein, called the wild-type, to construct a family of homologous proteins and study their properties.…
The interconnected processes of protein folding, mutations, epistasis, and evolution have all been the subject of extensive analysis throughout the years due to their significance for structural and evolutionary biology. The origin…
Protein folding and evolution are intimately linked phenomena. Here, we revisit the concept of exons as potential protein folding modules across 38 abundant and conserved protein families. Taking advantage of genomic exon-intron…
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,…
We propose an application of molecular information theory to analyze the folding of single domain proteins. We analyze results from various areas of protein science, such as sequence-based potentials, reduced amino acid alphabets, backbone…
Whether evolution can be predicted is a key question in evolutionary biology. Here we set out to better understand the repeatability of evolution. We explored experimentally the effect of mutation supply and the strength of selective…
Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the…
Selection pressures on proteins are usually measured by comparing homologous nucleotide sequences (Zuckerkandl and Pauling 1965). Recently we introduced a novel method, termed `volatility', to estimate selection pressures on protein…
We adopt the point of view that analysis of the stability of the protein folding process is central to understanding the underlying physics of folding. Stability of the folding process means that many perturbations do not disrupt the…
For the vast majority of naturally occurring, small, single domain proteins folding is often described as a two-state process that lacks detectable intermediates. This observation has often been rationalized on the basis of a nucleation…
Most amino acids are encoded by multiple synonymous codons. For an amino acid, some of its synonymous codons are used much more rarely than others. Analyses of positions of such rare codons in protein sequences revealed that rare codons can…