Related papers: Allo-network drugs: harnessing allostery in cellul…
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…
Despite improved rational drug design and a remarkable progress in genomic, proteomic and high-throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade. Multi-target drugs…
Recently, a number of drug-therapy, disease, drug, and drug-target networks have been introduced. Here we suggest novel methods for network-based prediction of novel drug targets and for improvement of drug efficiency by analysing the…
Allostery is a form of protein regulation, where ligands that bind sites located apart from the active site can modify the activity of the protein. The molecular mechanisms of allostery have been extensively studied, because allosteric…
Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding…
Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. Network…
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…
Despite considerable progress in genome- and proteome-based high-throughput screening methods and rational drug design, the number of successful single target drugs did not increase appreciably during the past decade. Network models suggest…
Network science is already making an impact on the study of complex systems and offers a promising variety of tools to understand their formation and evolution (1-4) in many disparate fields from large communication networks (5,6),…
Naively, one expects the information communicated by an enzyme downstream within a signaling network, in which the enzyme is embedded, to grow monotonically with the enzyme's rate of product formation. However, here we observe that this…
Drug repositioning offers an effective solution to drug discovery, saving both time and resources by finding new indications for existing drugs. Typically, a drug takes effect via its protein targets in the cell. As a result, it is…
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 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…
Recent advances in designing meta-materials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally-efficient…
Disordered elastic networks are a model material system in which it is possible to achieve tunable and trainable functions. This work investigates the modification of local mechanical properties in disordered networks inspired by allosteric…
Repurposing existing drugs to treat new diseases is a cost-effective alternative to de novo drug development, but there are millions of potential drug-disease combinations to be considered with only a small fraction being viable. In silico…
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…
Cells are regulated by networks of controllers having many targets, and targets affected by many controllers, but these "many-to-many" combinatorial control systems are poorly understood. Here we analyze distinct cellular networks…
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…
Drug combination refers to the use of two or more drugs to treat a specific disease at the same time. It is currently the mainstream way to treat complex diseases. Compared with single drugs, drug combinations have better efficacy and can…