Related papers: Proteins Evolution Upon Point Mutations
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
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…
Knotted proteins embed a physical (i.e., open) knot within their native structures. For decades, significant effort has been devoted to elucidating the functional role of knots in proteins, yet no consensus has been reached. Here, using…
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…
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…
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…
By balancing the average energy gap with its typical change due to mutations for protein-like heteropolymers with M residues, we show that native states are unstable to mutations on a scale M* ~ (lambda/sigma_mu)^(1/zeta_s), where lambda is…
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 regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks…
Understanding how monomeric proteins fold under in vitro conditions is crucial to describing their functions in the cellular context. Significant advances both in theory and experiments have resulted in a conceptual framework for describing…
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…
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…
We simulate neutral evolution of proteins imposing conservation of the thermodynamic stability of the native state in the framework of an effective model of folding thermodynamics. This procedure generates evolutionary trajectories in…
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…
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…
Stabilizing proteins is a foundational step in protein engineering. However, the evolutionary pressure of all extant proteins makes identifying the scarce number of mutations that will improve thermodynamic stability challenging. Deep…
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…
In the protein sequence space, natural proteins form clusters of families which are characterized by their unique native folds whereas the great majority of random polypeptides are neither clustered nor foldable to unique structures. Since…
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…
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…