相关论文: Soluble oligomerization provides a beneficial fitn…

Protein function often involves changes between different conformations. Central questions are how these conformational changes are coupled to the binding or catalytic processes during which they occur, and how they affect the catalytic…

Fitness effects of mutations fall on a continuum ranging from lethal to deleterious to beneficial. The distribution of fitness effects (DFE) among random mutations is an essential component of every evolutionary model and a mathematical…

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 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…

Genetic inactivation of essential genes creates an evolutionary scenario distinct from escape from drug inhibition, but the mechanisms of microbe adaptations in such cases remain unknown. Here we inactivate E. coli dihydrofolate reductase…

When polygenic traits are under stabilizing selection, many different combinations of alleles allow close adaptation to the optimum. If alleles have equal effects, all combinations that result in the same deviation from the optimum are…

Here we study how mutations which change physical properties of cell proteins (stability) impact population survival and growth. In our model the genotype is presented as a set of N numbers, folding free energies of cells N proteins.…

The importance of individual cells in a developing multicellular organism is well known but precisely how the individual cellular characteristics of those cells collectively drive the emergence of robust, homeostatic structures is less well…

Proteins are only moderately stable. It has long been debated whether this narrow range of stabilities is solely a result of neutral drift towards lower stability or purifying selection against excess stability is also at work - for which…

The relationship between sequence variation and phenotype is poorly understood. Here we use metabolomic analysis to elucidate the molecular mechanism underlying the filamentous phenotype of E. coli strains that carry destabilizing mutations…

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…

A basic question of protein structural studies is to which extent mutations affect the stability. This question may be addressed starting from sequence and/or from structure. In proteomics and genomics studies prediction of protein…

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…

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability requirement and the capacity of a protein to…

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…

Protein folding produces characteristic and functional three-dimensional structures from unfolded polypeptides or disordered coils. The emergence of extraordinary complexity in the protein folding process poses astonishing challenges to…

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…

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…

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…