相关论文: Stability Threshold as a Selection Principle for P…
The aim of this work is to elucidate how physical principles of protein design are reflected in natural sequences that evolved in response to the thermal conditions of the environment. Using an exactly solvable lattice model, we design…
The stability of model proteins with designed sequences is assessed in terms of the number of sequences (obtained from the designed sequence through mutations), which fold into 5the ``native'' conformation. By a complete enumeration of the…
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…
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…
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…
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,…
We review and further develop an analytical model that describes how thermodynamic constraints on the stability of the native state influence protein evolution in a site-specific manner. To this end, we represent both protein sequences and…
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…
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 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…
How typical elements that shape organisms, such as protein secondary structures, have evolved, or how evolutionarily susceptible/resistant they are to environmental changes, are significant issues in evolutionary biology, structural…
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…
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 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…
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,''…
Classical population genetics a priori assigns fitness to alleles without considering molecular or functional properties of proteins that these alleles encode. Here we study population dynamics in a model where fitness can be inferred from…
We derive an analytic expression for site-specific stationary distributions of amino acids from the Structurally Constrained Neutral (SCN) model of protein evolution with conservation of folding stability. The stationary distributions that…
Naturally evolving proteins gradually accumulate mutations while continuing to fold to thermodynamically stable native structures. This process of neutral protein evolution is an important mode of genetic change, and forms the basis for the…
The differing ability of polypeptide conformations to act as the native state of proteins has long been rationalized in terms of differing kinetic accessibility or thermodynamic stability. Building on the successful applications of physical…
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…