Related papers: Coarse-grained molecular simulations of allosteric…
Calmodulin (CaM) is a ubiquitous calcium binding protein consisting of two structurally similar domains with distinct stabilities, binding affinities, and flexibilities. We present coarse grained simulations that suggest the mechanism for…
We explore how inherent flexibility of a protein molecule influences the mechanism controlling the kinetics of allosteric transitions using a variational model inspired from work in protein folding. The striking differences in the predicted…
The key to understanding a protein's function often lies in its conformational dynamics. We develop a coarse-grained variational model to investigate the interplay between structural transitions, conformational flexibility and function of…
In allosteric proteins, binding a ligand can affect function at a distant location, for example by changing the binding affinity of a substrate at the active site. The induced fit and population shift models, which differ by the assumed…
The flexibility in the structure of calmodulin (CaM) allows its binding to over 300 target proteins in the cell. To investigate the structure-function relationship of CaM, we combined methods of computer simulation and experiments based on…
Large protein assemblies, such as virus capsids, may be coarse-grained as a set of rigid domains linked by generalized (rotational and stretching) harmonic springs. We present a method to obtain the elastic parameters and overdamped…
We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a…
The original ideas of Cooper and Dryden, that allosteric signalling can be induced between distant binding sites on proteins without any change in mean structural conformation, has proved to be a remarkably prescient insight into the rich…
We introduce an approach for performing "very long" computer simulations of the dynamics of simplified, folded proteins. Using an alpha-carbon protein model and a fine grid to mimic continuum computations at increased speed, we perform…
Proteins' fuzziness are features for communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene…
Elastic networks can be tuned to exhibit complex mechanical responses and have been extensively used to study protein allosteric functionality, where a localized strain regulates the conformation at a distant site. We show that cooperative…
A growing number of experimental evidence shows that it is general for a ligand binding protein to have a potential for allosteric regulation and for further evolution. In addition, such proteins generically change their conformation upon…
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…
We discuss theoretical models for the cooperative binding dynamics of ligands to substrates, such as dimeric motor proteins to microtubules or more extended macromolecules like tropomyosin to actin filaments. We study the effects of steric…
What are the molecular mechanisms that dictate protein-protein binding stability and whether those are related to the ones behind protein fold stability are still largely open questions. Indeed, despite many past efforts, we still lack…
This study reveals the essence of ligand recognition mechanisms by which calmodulin (CaM) controls a variety of Ca2+ signaling processes. We study eight forms of calcium-loaded CaM each with distinct conformational states. Reducing the…
Calmodulin, the ubiquitous calcium-activated second messenger in eukaryotes, is an extremely versatile molecule involved in many biological processes: muscular contraction, synaptic plasticity, circadian rhythm, and cell cycle, among…
Protein-ligand binding is the process by which a small molecule (drug or inhibitor) attaches to a target protein. Binding affinity, which characterizes the strength of biomolecular interactions, is essential for tackling diverse challenges…
Studying the conformations involved in the dimerization of cadherins is highly relevant to understand the development of tissue and its failure, which is associated with tumors and metastases. Experimental techniques, like X-ray…
Transitions between different conformational states are ubiquitous in proteins, being involved in signaling, catalysis and other fundamental activities in cells. However, modeling those processes is extremely difficult, due to the need of…