相关论文: Direct Coupling Analysis of Epistasis in Allosteri…
Various approaches have explored the covariation of residues in multiple-sequence alignments of homologous proteins to extract functional and structural information. Among those are principal component analysis (PCA), which identifies the…
Epistasis, or the context-dependence of the effects of mutations, limits our ability to predict the functional impact of combinations of mutations, and ultimately our ability to predict evolutionary trajectories. Information about the…
ATPases cyclically convert chemical energy in the form of ATP gradients into directed motion inside cells. To function, ATPases rely on allosteric communication between at least two binding sites, an internal signaling mechanism that is not…
Allostery is a fundamental property of proteins that represents the functional coupling between distantly located sites. In different manifestations, this property underlies signal transduction, gene expression, and regulation -- elementary…
Allosteric interactions occur when binding at one part of a complex affects the interactions at another part. Allostery offers a high degree of control in multi-species processes, and these interactions play a crucial role in many…
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…
Spatially proximate amino acids in a protein tend to coevolve. A protein's three-dimensional (3D) structure hence leaves an echo of correlations in the evolutionary record. Reverse engineering 3D structures from such correlations is an open…
Allosteric regulation in proteins is often accompanied by conformational changes that facilitate transmission of mechanical signals between distant ligand binding sites. Typically, these deformations are classified in terms of specific…
Allosteric interactions between molecules bound to DNA at distant locations have been known for a long time. The phenomenon has been studied via experiments and numerical simulations, but a comprehensive understanding grounded in a theory…
Determining which proteins interact together is crucial to a systems-level understanding of the cell. Recently, algorithms based on Direct Coupling Analysis (DCA) pairwise maximum-entropy models have allowed to identify interaction partners…
We introduce a data-driven epistatic model of protein evolution, capable of generating evolutionary trajectories spanning very different time scales reaching from individual mutations to diverged homologs. Our in silico evolution…
Protein contacts contain important information for protein structure and functional study, but contact prediction from sequence information remains very challenging. Recently evolutionary coupling (EC) analysis, which predicts contacts by…
Allosteric signaling in biological molecules, which may be viewed as specific action at a distance due to localized perturbation upon binding of ligands or changes in environmental cues, is pervasive in biology. Phenomenological MWC and KNF…
Allosteric regulation at distant sites is central to many cellular processes. In particular, allosteric sites in proteins are a major target to increase the range and selectivity of new drugs, and there is a need for methods capable of…
Epistasis refers to the phenomenon in which phenotypic consequences caused by mutation of one gene depend on one or more mutations at another gene. Epistasis is critical for understanding many genetic and evolutionary processes, including…
Many signalling functions in molecular biology require proteins bind to substrates such as DNA in response to environmental signals such as the simultaneous binding to a small molecule. Examples are repressor proteins which may transmit…
Allostery, the phenomenon by which the perturbation of a molecule at one site alters its behavior at a remote functional site, enables control over biomolecular function. Allosteric modulation is a promising avenue for drug discovery and is…
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
Elastic interactions arising from a difference of lattice spacing between two coherent phases can have a strong influence on the phase separation (coarsening) of alloys. If the elastic moduli are different in the two phases, the elastic…
The multiple sequence alignment (MSA) of a protein family provides a wealth of information in terms of the conservation pattern of amino acid residues not only at each alignment site but also between distant sites. In order to statistically…