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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

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

It is challenging to parameterize the force field for calcium ions (Ca2+) in calcium-binding proteins because of their unique coordination chemistry that involves the surrounding atoms required for stability. In this work, we observed wide…

Biomolecules · Quantitative Biology 2021-08-03 Pengzhi Zhang , Jaebeom Han , Piotr Cieplak , Margaret. S. Cheung

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…

Molecular Networks · Quantitative Biology 2015-06-19 Massimo Lai , Denis Brun , Stuart J Edelstein , Nicolas Le Novère

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

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

Protein dynamics in cells may be different from that in dilute solutions in vitro since the environment in cells is highly concentrated with other macromolecules. This volume exclusion due to macromolecular crowding is predicted to affect…

Biomolecules · Quantitative Biology 2009-11-13 Dirar Homouz , Loren Stagg , Pernilla Wittung-Stafshede , Margaret S. Cheung

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

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

Macromolecular crowding affects biophysical processes as diverse as diffusion, gene expression, cell growth, and senescence. Yet, there is no comprehensive understanding of how crowding affects reactions, particularly multivalent binding.…

Soft Condensed Matter · Physics 2024-01-15 Tomasz Skóra , Mathijs Janssen , Andreas Carlson , Svyatoslav Kondrat

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

Biomolecular condensates are essential for cellular organization and result from phase separation in systems far from thermodynamic equilibrium. Among various models, chemically active droplets play a significant role, consisting of…

Soft Condensed Matter · Physics 2025-05-19 Jacques Fries , Roxanne Berthin , Chengjie Luo , Marie Jardat , David Zwicker , Vincent Dahirel , Pierre Illien

Macromolecular crowding plays a principal role in a wide range of biological processes including gene expression, chromosomal compaction, and viral infection. However, the impact that crowding has on the dynamics of nucleic acids remains a…

In the cell, protein complexes form relying on specific interactions between their monomers. Excluded volume effects due to molecular crowding would lead to correlations between molecules even without specific interactions. What is the…

Soft Condensed Matter · Physics 2015-05-13 Wei Wang , Wei-Xin Xu , Y. Levy , E. Trizac , P. G. Wolynes

The cytoplasm of a living cell is crowded with several macromolecules of different shapes and sizes. Molecular diffusion in such a medium becomes anomalous due to the presence of macromolecules and diffusivity is expected to decrease with…

Statistical Mechanics · Physics 2009-11-13 Manish Agrawal , S. B. Santra , Rajat Anand , Rajaram Swaminathan

Macromolecular crowding plays a crucial role in modulating protein dynamics in cellular and in vitro environments. Polymeric crowders such as dextran and Ficoll are known to induce entropic forces, including depletion interactions, that…

Cell migration in fibreous extracellular matrix (ECM) is crucial to many physiological and pathological processes such as tissue regeneration, immune response and cancer progression. During migration, individual cells can generate active…

Cell Behavior · Quantitative Biology 2019-10-16 Yu Zheng , Hanqing Nan , Qihui Fan , Xiaochen Wang , Liyu Liu , Ruchuan Liu , Fangfu Ye , Bo Sun , Yang Jiao

We study the role of active coupling on the transport properties of homogeneously charged macromolecules in an infinitely dilute solution. An enzyme becomes actively bound to a segment of the macromolecule, exerting an electrostatic force…

Soft Condensed Matter · Physics 2024-05-24 Tapas Singha , Siao-Fong Li , Murugappan Muthukumar

The spatial organization of cell membrane glycoproteins and glycolipids is critical for mediating the binding of ligands, receptors, and macromolecules on the plasma membrane. However, we currently do not have the methods to quantify the…

Biological Physics · Physics 2023-06-21 Daniel P. Arnold , Yaxin Xu , Sho C. Takatori
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