Related papers: The Origin of Mutational Epistasis
This piece serves two purposes. Firstly, it aims at elucidating the role of epistasis in shaping, at a molecular level, the evolutionary paths of proteins, as well as the extent to which these epistatic effects are the outcome of an…
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,…
The fitness contribution of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations under selection, and can shape the…
Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish…
Since protein mutations are the main driving force of evolution at the molecular level, a proper analysis of them (and the factors controlling them) will enable us to find a response to several crucial queries in evolutionary biology. Among…
The primary aim of this work is to explore how proteins point mutations impact their marginal stability and, hence, their evolvability. With this purpose, we show that the use of four classic notions, namely, those from Leibniz & Kant…
The contribution to an organism's phenotype from one genetic locus may depend upon the status of other loci. Such epistatic interactions among loci are now recognized as fundamental to shaping the process of adaptation in evolving…
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…
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…
Introduction: While the origin and evolution of proteins remain mysterious, advances in evolutionary genomics and systems biology are facilitating the historical exploration of the structure, function and organization of proteins and…
These lectures will address two questions. Is there a simple variational principle underlying the existence of secondary motifs in the native state of proteins? Is there a general approach which can qualitatively capture the salient…
The protein folding problem has attracted an increasing attention from physicists. The problem has a flavor of statistical mechanics, but possesses the most common feature of most biological problems -- the profound effects of evolution. I…
Epistasis refers to the phenomenon in which phenotypic consequences caused by mutation of one gene depend on one or more mutations at another gene. Epistasis is critical for understanding many genetic and evolutionary processes, including…
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…
Epistatic interactions between mutations add substantial complexity to adaptive landscapes, and are often thought of as detrimental to our ability to predict evolution. Yet, patterns of global epistasis, in which the fitness effect of a…
Genetic interactions can strongly influence the fitness effects of individual mutations, yet the impact of these epistatic interactions on evolutionary dynamics remains poorly understood. Here we investigate the evolutionary role of…
Folding and aggregation of proteins, the interaction between proteins and membranes, as well as the adsorption of organic soft matter to inorganic solid substrates belong to the most interesting challenges in understanding structure and…
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…
How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…
Proteins, by virtue of their central role in most biological processes, represent one of the key subjects of the study of molecular evolution. Inherent to the indispensability of proteins for living cells is the fact that a given protein…