Related papers: The Origin of Mutational Epistasis
In evolution, the effects of a single deleterious mutation can sometimes be compensated for by a second mutation which recovers the original phenotype. Such epistatic interactions have implications for the structure of genome space -…
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…
The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon…
The protein folding is regarded as a quantum transition between torsion states on polypeptide chain. The deduction of the folding rate formula in our previous studies is reviewed. The rate formula is generalized to the case of frequency…
As an example of topic where biology and physics meet, we present the issue of protein folding and stability, and the development of thermodynamics-based bioinformatics tools that predict the stability and thermal resistance of proteins and…
Living systems evolve one mutation at a time, but a single mutation can alter the effect of subsequent mutations. The underlying mechanistic determinants of such epistasis are unclear. Here, we demonstrate that the physical dynamics of a…
The evolutionary origins of ageing and age-associated diseases continue to pose a fundamental question in biology. This study is concerned with a recently proposed framework, which conceptualises development and ageing as a continuous…
Protein fitness landscapes frequently exhibit epistasis, where the effect of a mutation depends on the genetic context in which it occurs, i.e., the rest of the protein sequence. Epistasis increases landscape complexity, often resulting in…
We review the background, theory and general equations for the analysis of equilibrium protein unfolding experiments, focusing on denaturant and heat-induced unfolding. The primary focus is on the thermodynamics of reversible…
Emergence of new protein structures has proved difficult to trace in nature and engineer in the laboratory. However, one aspect of structure evolution has proved immensely helpful for determining the three-dimensional structure of proteins…
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…
We develop a theoretical approach to the protein folding problem based on out-of-equilibrium stochastic dynamics. Within this framework, the computational difficulties related to the existence of large time scale gaps in the protein folding…
Many aspects of the study of protein folding and dynamics have been affected by the recent advances in machine learning. Methods for the prediction of protein structures from their sequences are now heavily based on machine learning tools.…
Evolution is a dynamic process. The two classical forces of evolution are mutation and selection. Assuming small mutation rates, evolution can be predicted based solely on the fitness differences between phenotypes. Predicting an…
It is well known amongst molecular biologists that proteins with a common ancestor and that perform the same function in similar organisms, can have rather different amino-acid sequences. Mutations have altered the amino-acid sequences…
The energy for protein folding arises from multiple sources and is not large in total. In spite of the many specific successes of energy landscape and other approaches, there still seems to be some missing guiding factor that explains how…
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…
The premise of genetic analysis is that a causal link exists between phenotypic and allelic variation. Yet it has long been documented that mutant phenotypes are not a simple result of a single DNA lesion, but rather are due to interactions…
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…
Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness…