Search arXiv⌕ Search
Home/Archive/arXiv

arXiv · 1510.08931

Comparing allosteric transitions in the domains of calmodulin through coarse-grained simulations

Prithviraj Nandigrami·John J. Portman
View original source ↗Read source document ↗Export metadata ↓

Abstract

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 the domain's allosteric transitions between the open and closed conformations depend on subtle differences in the folded state topology of the two domains. Throughout a wide temperature range, the simulated transition mechanism of the N-terminal domain (nCaM) follows a two-state transition mechanism while domain opening in the C-terminal domain (cCaM) involves unfolding and refolding of the tertiary structure. The appearance of the unfolded intermediate occurs at a higher temperature in nCaM than it does in cCaM consistent with nCaM's higher thermal stability. Under approximate physiological conditions, the simulated unfolded state population of cCaM accounts for 10% of the population with nearly all of the sampled transitions (approximately 95%) unfolding and refolding during the conformational change. Transient unfolding significantly slows the domain opening and closing rates of cCaM. This potentially influences the mechanism of calcium binding to each domain.

Explore related subjects

physics.bio-phq-bio.BM

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Prithviraj Nandigrami, John J. Portman. 2016-03-04. Comparing allosteric transitions in the domains of calmodulin through coarse-grained simulations. https://doi.org/10.1063/1.4943130

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Tracking and distinguishing slime mold solutions to traveling salesperson problems through synchronized amplification in the non-equilibrium steady state

The plasmodium of the true slime mold Physarum polycephalum-an ancient, unicellular, aneural organism-serves as a platform for studying the information-processing capacities of active matter. Previous experiments used Physarum's intricate morphological dynamics and photoavoidance in stellate chips to solve $N$-city traveling salesperson problems (TSPs) of up to eight cities, scaling linearly in time with TSP size. Optical feedback controlled by a modified Hopfield network illuminated specific lanes at regular intervals, prompting Physarum to elongate or retract selected branches. When the illumination pattern stabilized in a non-equilibrium steady state, branches bifurcated reproducibly into solution and non-solution groups, with the former exhibiting lower-frequency, higher-amplitude, and more synchronized oscillations than the latter across 41 trials with valid TSP solutions. Physarum's synchronization dynamics efficiently predict 100% of selected solutions by the midpoint of the optical-feedback interval, achieving statistically significant (paired t-test, $p<0.005$) discrimination from alternate tours well before the non-equilibrium steady state. Observed frequency downconversions and synchronized power amplifications scale linearly and quadratically, respectively, for small-to-moderate TSP size, as captured by a toy model of energy redistribution with saturating optical absorption. Tuning these features in native biomolecular chromophore networks may thus improve both the quality and efficiency of TSP solutions from Physarum-based biocomputers, which exploit the effects of organismal-scale coherence.

physics.bio-ph↗
arXiv2026

How do incorrect ligands help detect a correct ligand?

Intrigued by the response of T cell receptors to the presence of a few agonist ligands, we propose a minimal model that can achieve similar performance. The model consists of a small cluster of immobile receptors that bind reversibly to two types (correct/incorrect) of ligands in the environment, with slightly weaker binding strength for the incorrect one. It features binding-state coupling between nearest-neighbor receptors, and receptors in the bound/free states are activated/deactivated by specific enzymes, with rates that allow kinetic proofreading. It is found that, for a range of binding-state coupling strength, incorrect ligands alone cannot activate the receptors, but the binding of merely one correct ligand to a receptor is sufficient to promote the activation of other receptors via induced binding to incorrect ligands. Both response time and signal amplification increase as the receptor binding-state coupling strength increases until it reaches an optimal range to achieve the most rapid and sensitive response. These results suggest a possible mechanism for a speedy and specific response of receptors to very few correct ligands in biological and artificial systems at the subcellular scale.

physics.bio-ph↗
arXiv2026

Signature of mechanically induced cell extrusions in cell size distribution

How a growing tissue organizes its own homeostatic state is a central question in the physics of living matter. We show that when a growing epithelial sheet counteracts increasing cell density by mechanically squeezing cells out of its plane, a homeostatic in-plane pressure emerges as a generalization of a yield stress. We find that in the quasistatic growth limit the homeostatic state is marginally stable, with a pseudogap in the distribution of local distances to the extrusion threshold pressure. Because such mechanically induced extrusions arise from an instability of individual cells, the pseudogap is imprinted in the distribution of cell areas. This provides an image-based way to test for presence of mechanically induced extrusions and we identify this signature in the developing wing epithelium of \textit{D.~melanogaster}. We expect the same principles to apply to confined three-dimensional tissues.

physics.bio-ph↗