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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…

Biomolecules · Quantitative Biology 2015-05-28 Qian Wang , Kao-Chen Liang , Arkadiusz Czader , M. Neal Waxham , Margaret S. Cheung

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…

Biological Physics · Physics 2016-03-14 Prithviraj Nandigrami , John J. Portman

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…

Biological Physics · Physics 2011-07-12 Ali Rana Atilgan , Ayse Ozlem Aykut , Canan Atilgan

The ATP-driven Plasma Membrane Calcium pump or Ca(2+)-ATPase (PMCA) is characterized by a high affinity to calcium and a low transport rate compared to other transmembrane calcium transport proteins. It plays a crucial role for calcium…

Biological Physics · Physics 2014-11-18 Michael Graupner , Frido Erler , Michael Meyer-Hermann

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…

Quantitative Methods · Quantitative Biology 2008-07-10 Swarnendu Tripathi , John J. Portman

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…

Quantitative Methods · Quantitative Biology 2009-11-13 Swarnendu Tripathi , John J. Portman

Interactions between a protein and a ligand are often accompanied by a redistribution of the population of thermally accessible conformations. This dynamic response of the protein's functional energy landscape enables a protein to modulate…

Biological Physics · Physics 2016-03-15 Prithviraj Nandigrami , John J. Portman

Calcium is an ubiquitous second messenger that triggers a plethora of key physiological responses. The events are initiated in micro- or nano-sized compartments and determined by the complex interactions with calcium-binding proteins and…

Subcellular Processes · Quantitative Biology 2013-05-01 S. L. Mironov

Neurons rely on two interdependent mechanisms, homeostasis and neuromodulation, to maintain robust and adaptable functionality. Calcium homeostasis stabilizes neuronal activity by adjusting ionic conductances, whereas neuromodulation…

Neurons and Cognition · Quantitative Biology 2026-05-13 Arthur Fyon , Guillaume Drion

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…

Biological Physics · Physics 2007-05-23 Daniel M. Zuckerman

Mechanical unfolding of several domains of calmodulin and titin is studied using a Go-like model with a realistic contact map and Lennard-Jones contact interactions. It is shown that this simple model captures the experimentally observed…

Biomolecules · Quantitative Biology 2009-11-10 Marek Cieplak

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…

Chemical Physics · Physics 2019-05-15 Francesco Delfino , Yuri Porozov , Eugene Stepanov , Gaik Tamazian , Valentina Tozzini

Many cellular processes require a polarization axis which generally initially emerges as an inhomogeneous distribution of molecular markers in the cell. We present a simple analytical model of a general mechanism of cell polarization taking…

Cell Behavior · Quantitative Biology 2009-10-21 Rhoda J. Hawkins , Olivier Benichou , Matthieu Piel , Raphael Voituriez

Many cells use calcium signalling to carry information from the extracellular side of the plasma membrane to targets in their interior. Since virtually all cells employ a network of biochemical reactions for Ca2+ signalling, much effort has…

Neurons and Cognition · Quantitative Biology 2009-12-17 Maurizio De Pitta` , Vladislav Volman , Herbert Levine , Eshel Ben-Jacob

Astrocytes express a large variety of G~protein-coupled receptors (GPCRs) which mediate the transduction of extracellular signals into intracellular calcium responses. This transduction is provided by a complex network of biochemical…

Subcellular Processes · Quantitative Biology 2018-01-23 Maurizio De Pittà , Eshel Ben-Jacob , Hugues Berry

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…

Quantitative Methods · Quantitative Biology 2024-07-25 Pengzhi Zhang , Jules Nde , Yossi Eliaz , Nathaniel Jennings , Piotr Cieplak , Margaret. S. Cheung

Intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) govern a daunting number of physiological processes. For such proteins, molecular mechanisms governing their interactions with proteins…

Biomolecules · Quantitative Biology 2016-11-15 Erik C. Cook , Bin Sun , Peter M. Kekenes-Huskey , Trevor P Creamer

The complex dynamics of intracellular calcium regulates cellular responses to information encoded in extracellular signals. Here, we study the encoding of these external signals in the context of the Li-Rinzel model. We show that by control…

Cell Behavior · Quantitative Biology 2008-06-17 Maurizio De Pitta , Vladislav Volman , Herbert Levine , Giovanni Pioggia , Danilo De Rossi , Eshel Ben-Jacob

Eukaryotic cells adhere to extracellular matrix during the normal development of the organism, forming static adhesion as well as during cell motility. We study this process by considering a simplified coarse-grained model of a vesicle that…

Biological Physics · Physics 2021-01-05 Raj Kumar Sadhu , Samo Penič , Aleš Iglič , Nir S. Gov

In this letter we present the results of a simple model for intercellular communication via calcium oscillations, motivated in part by a recent experimental study. The model describes two cells (a "donor" and "sensor") whose intracellular…

Biological Physics · Physics 2007-05-23 M. E. Gracheva , J. D. Gunton
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