Related papers: Inferring protein folding mechanisms from natural …
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…
Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…
Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. Due to their symmetry, these proteins constitute excellent model systems to investigate how evolution relates to structure,…
In the protein sequence space, natural proteins form clusters of families which are characterized by their unique native folds whereas the great majority of random polypeptides are neither clustered nor foldable to unique structures. Since…
For the vast majority of naturally occurring, small, single domain proteins folding is often described as a two-state process that lacks detectable intermediates. This observation has often been rationalized on the basis of a nucleation…
How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…
While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information to predict the three--dimensional, biologically active, native conformation of…
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…
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…
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…
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…
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…
Geometric and structural constraints greatly restrict the selection of folds adapted by protein backbones, and yet, folded proteins show an astounding diversity in functionality. For structure to have any bearing on function, it is thus…
Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…
Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…
Natural protein sequences that self-assemble to form globular structures are compact with high packing densities in the folded states. It is known that proteins unfold upon addition of denaturants, adopting random coil structures. The…
Exploring and understanding the protein-folding problem has been a long-standing challenge in molecular biology. Here, using molecular dynamics simulation, we reveal how parallel distributed adjacent planar peptide groups of unfolded…
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…
We propose an application of molecular information theory to analyze the folding of single domain proteins. We analyze results from various areas of protein science, such as sequence-based potentials, reduced amino acid alphabets, backbone…
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…