Related papers: Revealing evolutionary constraints on proteins thr…
Amino acid sequence portrays most intrinsic form of a protein and expresses primary structure of protein. The order of amino acids in a sequence enables a protein to acquire a particular stable conformation that is responsible for the…
Protein sequence generation via stochastic attention produces plausible family members from small alignments without training, but treats all stored sequences equally and cannot direct generation toward a functional subset of interest. We…
The coding space of protein sequences is shaped by evolutionary constraints set by requirements of function and stability. We show that the coding space of a given protein family--the total number of sequences in that family--can be…
An important part of the analysis of bio-molecular networks is to detect different functional units. Different functions are reflected in a different evolutionary dynamics, and hence in different statistical characteristics of network…
AlphaFold2 (AF2) has transformed protein structure prediction by harnessing co-evolutionary constraints embedded in multiple sequence alignments (MSAs). MSAs not only encode static structural information, but also hold critical details…
The enormous size and complexity of genotypic sequence space frequently requires consideration of coarse-grained sequences in empirical models. We develop scaling relations to quantify the effect of this coarse-graining on properties of…
Protein folding and evolution are intimately linked phenomena. Here, we revisit the concept of exons as potential protein folding modules across 38 abundant and conserved protein families. Taking advantage of genomic exon-intron…
Computational protein design facilitates discovery of novel proteins with prescribed structure and functionality. Exciting designs were recently reported using novel data-driven methodologies that can be roughly divided into two categories:…
Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the…
Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…
We introduce a minimal model for the evolution of functional protein-interaction networks using a sequence-based mutational algorithm, and apply the model to study neutral drift in networks that yield oscillatory dynamics. Starting with a…
The evolutionary trajectory of a protein through sequence space is constrained by function and three-dimensional (3D) structure. Residues in spatial proximity tend to co-evolve, yet attempts to invert the evolutionary record to identify…
Evolution occurs in populations of reproducing individuals. The structure of a biological population affects which traits evolve. Understanding evolutionary game dynamics in structured populations is difficult. Precise results have been…
The alignment of biological sequences such as DNA, RNA, and proteins, is one of the basic tools that allow to detect evolutionary patterns, as well as functional/structural characterizations between homologous sequences in different…
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…
Several physical mechanisms have been proposed to explain allostery in proteins. They differ by the number of internal states that they assume a protein to occupy, leaving open the question of what controls the emergence of these distinct…
The mutation and selection of regulatory DNA sequences is presented as an ideal model system of molecular evolution where genotype, phenotype, and fitness can be explicitly and independently characterized. In this theoretical study, we…
We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…
The ability of a protein to recognise multiple independent target conformations was demonstrated in [1]. Here we consider the recognition of correlated configurations, which we apply to funnel design for a single conformation. The maximum…
Pre-trained models have been successful in many protein engineering tasks. Most notably, sequence-based models have achieved state-of-the-art performance on protein fitness prediction while structure-based models have been used…