Related papers: The Origin of Mutational Epistasis

We show that in experimental atomic force microscopy studies of the lifetime distribution of mechanically stressed folded proteins the effects of externally applied fluctuations can not be distinguished from those of internally present…

Viral capsids are structurally constrained by interactions amongst the amino acids of the constituting proteins. Therefore, epistasis is expected to evolve amongst sites engaged in physical interactions, and to influence their substitution…

Epistasis, or the context-dependence of the effects of mutations, limits our ability to predict the functional impact of combinations of mutations, and ultimately our ability to predict evolutionary trajectories. Information about the…

The prediction of the biologically active native conformation of a protein is one of the fundamental challenges of structural biology. This problem remains yet unsolved mainly due to three factors: the partial knowledge of the effective…

Recent experiments and simulations have demonstrated that proteins can fold on the ribosome. However, the extent and generality of fitness effects resulting from co-translational folding remain open questions. Here we report a genome-wide…

Traditionally evolution is seen as a process where from a pool of possible variations of a population (e.g. biological species or industrial goods) a few variations get selected which survive and proliferate, whereas the others vanish.…

Though the problem of sequence-reversed protein folding is largely unexplored, one might speculate that reversed native protein sequences should be significantly more foldable than purely random heteropolymer sequences. In this article, we…

A central challenge in the study of protein evolution is the identification of historic amino acid sequence changes responsible for creating novel functions observed in present-day proteins. To address this problem, we developed a new…

During their evolution, proteins explore sequence space via an interplay between random mutations and phenotypic selection. Here we build upon recent progress in reconstructing data-driven fitness landscapes for families of homologous…

Is evolution always gradual or can it make leaps? We examine a mathematical model of an evolutionary process on a fitness landscape and obtain analytic solutions for the probability of multi-mutation leaps, that is, several mutations…

Molecules provide the ultimate language in terms of which physiology and pathology must be understood. Myriads of proteins participate in elaborate networks of interactions and perform chemical activities coordinating the life of cells. To…

We simulate the evolution of a protein-like sequence subject to point mutations, imposing conservation of the ground state, thermodynamic stability and fast folding. Our model is aimed at describing neutral evolution of natural proteins. We…

The intricate three-dimensional geometries of protein tertiary structures underlie protein function and emerge through a folding process from one-dimensional chains of amino acids. The exact spatial sequence and configuration of amino…

We explicitly show the connection between the protein folding problem and spin glass transition. This is then used to identify appropriate quantities that are required to describe the transition. A possible way of observing the spin glass…

We discuss the problem of proteasomal degradation of proteins. Though proteasomes are important for all aspects of the cellular metabolism, some details of the physical mechanism of the process remain unknown. We introduce a stochastic…

A transfer-matrix formalism is introduced to evaluate exactly the partition function of the Munoz-Eaton model, relating the folding kinetics of proteins of known structure to their thermodynamics and topology. This technique can be used for…

Enzymes are on the front lines of evolution. All living organisms rely on highly efficient, specific enzymes for growth, sustenance, and reproduction; and many diseases are a consequence of a mutation on an enzyme that affects its catalytic…

The phenotypic consequences of individual mutations are modulated by the wild type genetic background in which they occur.Although such background dependence is widely observed, we do not know whether general patterns across species and…

Focusing on a small set of proteins that i) fold in a concerted, all-or-none fashion and ii) do not contain knots or slipknots, we show that the Gauss linking integral, the torsion and the number of sequence-distant contacts provide…

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…