Related papers: Revealing evolutionary constraints on proteins thr…
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…
In this paper, we address the problem of identifying protein functionality using the information contained in its aminoacid sequence. We propose a method to define sequence similarity relationships that can be used as input for…
In sexual populations, selection operates neither on the whole genome, which is repeatedly taken apart and reassembled by recombination, nor on individual alleles that are tightly linked to the chromosomal neighborhood. The resulting…
Emergence of new protein structures has proved difficult to trace in nature and engineer in the laboratory. However, one aspect of structure evolution has proved immensely helpful for determining the three-dimensional structure of proteins…
In this Communication we present statistical analysis of conservation profiles in families of homologous sequences for nine proteins whose folding nucleus was determined by protein engineering methods. We show that in all but one protein…
Recent experiments and simulations have demonstrated that proteins can fold on the ribosome. However, the extent and generality of fitness effects resulting from co-translational folding remain open questions. Here we report a genome-wide…
The structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein's sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral…
Evolutionary dynamics and patterns of molecular evolution are strongly influenced by selection on linked regions of the genome, but our quantitative understanding of these effects remains incomplete. Recent work has focused on predicting…
Prestrained elastic networks arise in a number of biological and technological systems ranging from the cytoskeleton of cells to tensegrity structures. To understand the response of such a network as a function of the prestrain, we consider…
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 evolution processes of complex systems carry key information in the systems' functional properties. Applying machine learning algorithms, we demonstrate that the historical formation process of various networked complex systems can be…
A Profile Mixture Model is a model of protein evolution, describing sequence data in which sites are assumed to follow many related substitution processes on a single evolutionary tree. The processes depend in part on different amino acid…
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…
Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution…
Our work is motivated by and illustrated with application of association networks in computational biology, specifically in the context of gene/protein regulatory networks. Association networks represent systems of interacting elements,…
Recent years have seen tremendous developments in the use of machine learning models to link amino acid sequence, structure and function of folded proteins. These methods are, however, rarely applicable to the wide range of proteins and…
The past decade has witnessed the development and success of coarse-grained network models of proteins for predicting many equilibrium properties related to collective modes of motion. Curiously, the results are usually robust towards the…
The promise of discovering a functional blueprint of a cellular system from large-scale and high-throughput sequence and experimental data is predicated on the belief that the same top-down investigative approach that proved successful in…
Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence…
Most amino acids are encoded by multiple synonymous codons. For an amino acid, some of its synonymous codons are used much more rarely than others. Analyses of positions of such rare codons in protein sequences revealed that rare codons can…