Related papers: Stability of Designed Proteins Against Mutations
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…
Native protein folds often have a high degree of symmetry. We study the relationship between the symmetries of native proteins, and their designabilities -- how many different sequences encode a given native structure. Using a…
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…
Only about 1,000 qualitatively different protein folds are believed to exist in nature. Here, we review theoretical studies which suggest that some folds are intrinsically more designable than others, {\it i.e.} are lowest energy states of…
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…
We review the recent progress in computational approaches to protein design which builds on advances in statistical-mechanical protein folding theory. In particular, we evaluate the degeneracy of the protein code (i.e. how many sequences…
Protein folds are highly designable, in the sense that many sequences fold to the same conformation. In the present work we derive an expression for the designability in a 20 letter lattice model of proteins which, relying only on the…
Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…
The sensitivity of the native states of protein-like heteropolymers to mutations modelled as perturbations in the interaction potential between amino acids is studied. The stability threshold against mutations is shown to be zero for random…
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…
Protein structures in nature often exhibit a high degree of regularity (secondary structures, tertiary symmetries, etc.) absent in random compact conformations. We demonstrate in a simple lattice model of protein folding that structural…
Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…
The time evolution of the formation probability of native bonds has been studied for designed sequences which fold fast into the native conformation. From this analysis a clear hierarchy of bonds emerge a) local, fast forming highly stable…
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…
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…
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…
The folding characteristics of sequences reduced with a possibly simplified representation of five types of residues are shown to be similar to their original ones with the natural set of residues (20 types or 20 letters). The reduced…
We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…
Monte Carlo simulations of a simple lattice model of protein folding show two distinct regimes depending on the chain length. The first regime well describes the folding of small protein sequences and its kinetic counterpart appears to be…
Protein sequences are believed to have been selected to provide the stability of, and reliable renaturation to, an encoded unique spatial fold. In recently proposed theoretical schemes, this selection is modeled as ``minimal frustration,''…