Related papers: Uncovering allosteric pathways in caspase-1 with M…
Allosteric regulation is central to many biochemical processes. Allosteric sites provide a target to fine-tune protein activity, yet we lack computational methods to predict them. Here, we present an efficient graph-theoretical approach for…
Allostery commonly refers to the mechanism that regulates protein activity through the binding of a molecule at a different, usually distal, site from the orthosteric site. The omnipresence of allosteric regulation in nature and its…
Aspartate carbamoyltransferase (ATCase) is a large dodecameric enzyme with six active sites that exhibits allostery: its catalytic rate is modulated by the binding of various substrates at distal points from the active sites. A recently…
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…
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…
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…
Understanding the link between structure and function in proteins is fundamental in molecular biology and proteomics. A central question in this context is whether allostery - where the binding of a molecule at one site affects the activity…
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…
G-protein coupled receptors (GPCRs), a major gatekeeper of extracellular signals on plasma membrane, are unarguably one of the most important therapeutic targets. Given the recent discoveries of allosteric modulations, an allosteric wiring…
Neurotensin receptor 1 (NTSR1), a member of the Class A G protein-coupled receptor superfamily, plays an important role in modulating dopaminergic neuronal activity and eliciting opioid-independent analgesia. Recent studies suggest that…
Determining the principal energy pathways for allosteric communication in biomolecules, that occur as a result of thermal motion, remains challenging due to the intrinsic complexity of the systems involved. Graph theory provides an approach…
Allosteric effects are often underlying the activity of proteins and elucidating generic design aspects and functional principles which are unique to allosteric phenomena represents a major challenge. Here an approach which consists in the…
Binding and unbinding of ligands to specific sites of a macromolecule are one of the most elementary molecular interactions inside the cell that embody the computational processes of biological regulations. The interaction between…
We present a new method that enables the identification and analysis of both transition and metastable conformational states from atomistic or coarse-grained molecular dynamics (MD) trajectories. Our algorithm is presented and studied by…
Allostery plays a crucial role in regulating protein activity, making it a highly sought-after target in drug development. One of the major challenges in allosteric drug research is the identification of allosteric sites. In recent years,…
In allosteric proteins, the binding of a ligand modifies function at a distant active site. Such allosteric pathways can be used as target for drug design, generating considerable interest in inferring them from sequence alignment data.…
Allostery refers to the puzzling phenomenon of long-range communication between distant sites in proteins. Despite its importance in biomolecular regulation and signal transduction, the underlying dynamical process is not well understood.…
Post-transductional modifications tune the functions of proteins and regulate the collective dynamics of biochemical networks that determine how cells respond to environmental signals. For example, protein phosphorylation and nitrosylation…
We present a method to sample Markov-chain trajectories constrained to both the initial and final conditions, which we term Markov bridges. The trajectories are conditioned to end in a specific state at a given time. We derive the master…
Allostery is a fundamental mechanism of protein regulation and is commonly interpreted as modulating enzymatic activity or product abundance. Here we show that this view is incomplete. Using a stochastic model of allosteric regulation…