Related papers: The Origin of Mutational Epistasis
While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information to predict the three--dimensional, biologically active, native conformation of…
An all-atom model of proteins is used to show that the same sequence of amino acids can have many alternative structures, that are very distant from, and that can be as stable as, the corresponding native structure. Such alternative…
Motivation: Protein folding is a dynamic process during which a protein's amino acid sequence undergoes a series of 3-dimensional (3D) conformational changes en route to reaching a native 3D structure; the resulting 3D structural…
We study the impact of mutations (changes in amino acid sequence) on the thermodynamics of simple protein-like heteropolymers consisting of N monomers, representing the amino acid sequence. The sequence is designed to fold into its native…
In this work, we discovered a fundamental connection between selection for protein stability and emergence of preferred structures of proteins. Using standard exact 3-dimensional lattice model we evolve sequences starting from random ones…
We investigated melting transitions in biological membranes in their native state that include their membrane proteins. These membranes originated from \textit{E. coli}, \textit{B. subtilis}, lung surfactant and nerve tissue from the spinal…
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…
How do mammalian cells that share the same genome exist in notably distinct phenotypes, exhibiting differences in morphology, gene expression patterns, and epigenetic chromatin statuses? Furthermore how do cells of different phenotypes…
A fundamental question for evolutionary biology is why rates of evolution vary dramatically between proteins. Perhaps surprisingly, it is controversial how much a protein's functional importance affects its rate of evolution. In most…
Motivated by present activities in (statistical) physics directed towards biological evolution, we review the interplay of three evolutionary forces: mutation, selection, and genetic drift. The review addresses itself to physicists and…
Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution…
One of the main concerns of Anfinsen was to reveal the connection between the amino acid sequence and their biologically active conformation. This search gave rise to two crucial questions in structural biology, namely, why the proteins…
The common understanding of protein evolution has been that neutral or slightly deleterious mutations are fixed by random drift, and evolutionary rate is determined primarily by the proportion of neutral mutations. However, recent studies…
BACKGROUND: Many of the mutations accumulated by naturally evolving proteins are neutral in the sense that they do not significantly alter a protein's ability to perform its primary biological function. However, new protein functions evolve…
Motivation: Site directed mutagenesis is widely used to understand the structure and function of biomolecules. Computational prediction of protein mutation impacts offers a fast, economical and potentially accurate alternative to laboratory…
Understanding of the evolutionary origins of protein structures represents a key component of the understanding of molecular evolution as a whole. Here we seek to elucidate how the features of an underlying protein structural "space" might…
The mutation rate of a well adapted population is prone to reduction so as to have a lower mutational load. We aim to understand the role of epistatic interactions between the fitness affecting mutations in this process. Using a multitype…
Protein folding is a universal process, very fast and accurate, which works consistently (as it should be) in a wide range of physiological conditions. The present work is based on three premises, namely: ($i$) folding reaction is a process…
The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…
Extensive Monte Carlo folding simulations for four proteins of various structural classes are carried out, using a single atomistic potential. In all cases, collapse occurs at a very early stage, and proteins fold into their native-like…