Related papers: The Origin of Mutational Epistasis
In epistatic fitness landscapes, the fitness effect of a mutation depends on the genetic background and may even switch between deleterious and beneficial depending on the presence of another mutation. Epistatic interactions may cause both…
Biases in molecular evolution can significantly influence evolutionary trajectories. They have been described in a variety of contexts such as development and mutation, but not for acquiring new functions (i.e. emergence). Here, we…
Epistatic interactions between residues determine a protein's adaptability and shape its evolutionary trajectory. When a protein experiences a changed environment, it is under strong selection to find a peak in the new fitness landscape. It…
A geometric analysis of protein folding, which complements many of the models in the literature, is presented. We examine the process from unfolded strand to the point where the strand becomes self-interacting. A central question is how it…
One of the most puzzling and unsolved challenges in molecular biology is understanding how proteins fold. Despite having advanced predictive tools that can accurately estimate the native structures of proteins, we still lack a comprehensive…
There is an intrinsic relationship between the molecular evolution in primordial period and the properties of genomes and proteomes of contemporary species. The genomic data may help us understand the driving force of evolution of life at…
Naturally evolving proteins gradually accumulate mutations while continuing to fold to thermodynamically stable native structures. This process of neutral protein evolution is an important mode of genetic change, and forms the basis for the…
BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar…
The next step in the understanding of the genome organization, after the determination of complete sequences, involves proteomics. The proteome includes the whole set of protein-protein interactions, and two recent independent studies have…
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,…
We simulate the evolution of model protein sequences subject to mutations. A mutation is considered neutral if it conserves 1) the structure of the ground state, 2) its thermodynamic stability and 3) its kinetic accessibility. All other…
Protein folding is a phenomenon that has been studied for about 50 years and still remains as an unsolved problem. The main feature of this process is that it occurs as an all or none process, so a protein, can jump directly between folded…
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…
Neither of the two prevalent theories, namely thermodynamic stability and kinetic stability, provides a comprehensive understanding of protein folding. The thermodynamic theory is misleading because it assumes that free energy is the…
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…
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…
Protein folding, peptide aggregation and crystallization, as well as adsorption of molecules on soft or solid substrates have an essential feature in common: In all these processes, structure formation is guided by a collective, cooperative…
We present a simple model of protein folding dynamics that captures key qualitative elements recently seen in all-atom simulations. The goals of this theory are to serve as a simple formalism for gaining deeper insight into the physical…
We discuss recent theoretical developments in the study of simple lattice models of proteins. Such models are designed to understand general features of protein structures and mechanism of folding. Among the topics covered are (i) the use…
Defining the extent of epistasis - the non-independence of the effects of mutations - is essential for understanding the relationship of genotype, phenotype, and fitness in biological systems. The applications cover many areas of biological…