Related papers: Stability and the Evolvability of Function in a Mo…
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…
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…
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…
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…
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…
The growing interest for comparing protein internal dynamics owes much to the realization that protein function can be accompanied or assisted by structural fluctuations and conformational changes. Analogously to the case of functional…
It is shown that a small subset of modes which are likely to be involved in protein functional motions of large amplitude can be determined by retaining the most robust normal modes obtained using different protein models. This result…
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…
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…
Making use of a simplified model for protein folding, it can be shown that conformations which are particularly stable when their energy is minimized with respect to amino acid sequence (in the sense that they display a large energy gap to…
The ability to absorb mutations while retaining structure and function, or mutational robustness, is a remarkable property of natural proteins. In this Letter, we use a computational model of organismic evolution [Zeldovich et al, PLOS Comp…
Cotranslational folding depends on the folding speed and stability of the nascent protein. It remains difficult, however, to predict which proteins cotranslationally fold. Here, we simulate evolution of model proteins to investigate how…
BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar…
Many native structures of proteins accomodate complex topological motifs such as knots, lassos, and other geometrical entanglements. How proteins can fold quickly even in the presence of such topological obstacles is a debated question in…
In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with…
In the framework of a lattice-model study of protein folding, we investigate the interplay between designability, thermodynamic stability, and kinetics. To be ``protein-like'', heteropolymers must be thermodynamically stable, stable against…
We present two simplified models of protein dynamics based on Langevin's equation of motion in a viscous medium. We explore the effect of the potential energy function's symmetry on the kinetics and thermodynamics of simulated folding. We…
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…
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…
The functionality of protein-protein complexes is closely tied to the strength of their interactions, making the evaluation of binding affinity a central focus in structural biology. However, the molecular determinants underlying binding…