Statistical Analyses and Theoretical Models of Single-Molecule Enzymatic Dynamics

1999 ◽  
Vol 103 (49) ◽  
pp. 10477-10488 ◽  
Author(s):  
Gregory K. Schenter ◽  
H. Peter Lu ◽  
X. Sunney Xie
Keyword(s):  
Single Molecule ◽  
Theoretical Models ◽  
Statistical Analyses

Three-state molecular potentiometer based on a non-symmetrically positioned in-backbone linker

2021 ◽  
Author(s):  
Lucia Palomino-Ruiz ◽  
Pablo Reiné ◽  
Irene R. Marquez ◽  
Luis Alvarez de Cienfuegos ◽  
Nicolas Agrait ◽  
...  
Keyword(s):  
Single Molecule ◽  
Theoretical Models ◽  
Phenylene Ethynylene ◽  
Conductance States

We report on the synthesis and single-molecule conductance of a para-oligo(phenylene)ethynylene (p-OPE) derivative with three well-defined conductance states. Employing theoretical models and comparing to reference compounds we show that this...

scholarly journals Single-molecule diffusometry reveals no catalysis-induced diffusion enhancement of alkaline phosphatase as proposed by FCS experiments

2020 ◽  
Vol 117 (35) ◽  
pp. 21328-21335
Author(s):  
Zhijie Chen ◽  
Alan Shaw ◽  
Hugh Wilson ◽  
Maxime Woringer ◽  
Xavier Darzacq ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Single Molecule ◽  
Particle Tracking ◽  
Single Particle ◽  
Theoretical Models ◽  
Single Particle Tracking ◽  
Correlation Spectroscopy ◽  
Single Molecule Level ◽  
Diffusion Phenomena ◽  
Diffusion Enhancement

Theoretical and experimental observations that catalysis enhances the diffusion of enzymes have generated exciting implications about nanoscale energy flow, molecular chemotaxis, and self-powered nanomachines. However, contradictory claims on the origin, magnitude, and consequence of this phenomenon continue to arise. To date, experimental observations of catalysis-enhanced enzyme diffusion have relied almost exclusively on fluorescence correlation spectroscopy (FCS), a technique that provides only indirect, ensemble-averaged measurements of diffusion behavior. Here, using an anti-Brownian electrokinetic (ABEL) trap and in-solution single-particle tracking, we show that catalysis does not increase the diffusion of alkaline phosphatase (ALP) at the single-molecule level, in sharp contrast to the ∼20% enhancement seen in parallel FCS experiments usingp-nitrophenyl phosphate (pNPP) as substrate. Combining comprehensive FCS controls, ABEL trap, surface-based single-molecule fluorescence, and Monte Carlo simulations, we establish thatpNPP-induced dye blinking at the ∼10-ms timescale is responsible for the apparent diffusion enhancement seen in FCS. Our observations urge a crucial revisit of various experimental findings and theoretical models––including those of our own––in the field, and indicate that in-solution single-particle tracking and ABEL trap are more reliable means to investigate diffusion phenomena at the nanoscale.

scholarly journals Insights into the origin of the high energy-conversion efficiency of F1-ATPase

2019 ◽  
Vol 116 (32) ◽  
pp. 15924-15929 ◽  
Author(s):  
Kwangho Nam ◽  
Martin Karplus
Keyword(s):  
Single Molecule ◽  
Atp Hydrolysis ◽  
Theoretical Models ◽  
Adenosine Diphosphate ◽  
Energy Conversion Efficiency ◽  
High Energy ◽  
Structural Deformation ◽  
Coupling Mechanism ◽  
Surprising Result ◽  
X Ray Crystallography

Our understanding of the rotary-coupling mechanism of F1-ATPase has been greatly enhanced in the last decade by advances in X-ray crystallography, single-molecular imaging, and theoretical models. Recently, Volkán-Kacsó and Marcus [S. Volkán-Kacsó, R. A. Marcus, Proc. Natl. Acad. Sci. U.S.A. 112, 14230 (2015)] presented an insightful thermodynamic model based on the Marcus reaction theory coupled with an elastic structural deformation term to explain the observed γ-rotation angle dependence of the adenosine triphosphate (ATP)/adenosine diphosphate (ADP) exchange rates of F1-ATPase. Although the model is successful in correlating single-molecule data, it is not in agreement with the available theoretical results. We describe a revision of the model, which leads to consistency with the simulation results and other experimental data on the F1-ATPase rotor compliance. Although the free energy liberated on ATP hydrolysis by F1-ATPase is rapidly dissipated as heat and so cannot contribute directly to the rotation, we show how, nevertheless, F1-ATPase functions near the maximum possible efficiency. This surprising result is a consequence of the differential binding of ATP and its hydrolysis products ADP and Pi along a well-defined pathway.

scholarly journals Theoretical models for single-molecule DNA and RNA experiments: from elasticity to unzipping

2002 ◽  
Vol 3 (5) ◽  
pp. 569-584 ◽  
Author(s):  
Simona Cocco ◽  
John F. Marko ◽  
Rémi Monasson
Keyword(s):  
Single Molecule ◽  
Theoretical Models ◽  
Dna And Rna

scholarly journals Nanomechanical Characterization of Amyloid Fibrils Using Single-Molecule Experiments and Computational Simulations

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Bumjoon Choi ◽  
Taehee Kim ◽  
Sang Woo Lee ◽  
Kilho Eom
Keyword(s):  
Mechanical Properties ◽  
Atomic Force Microscopy ◽  
Single Molecule ◽  
Amyloid Fibrils ◽  
Theoretical Models ◽  
Beam Model ◽  
Computational Simulations ◽  
Force Microscopy ◽  
Nanomechanical Properties ◽  
Atomic Force

Amyloid fibrils have recently received much attention due to not only their important role in disease pathogenesis but also their excellent mechanical properties, which are comparable to those of mechanically strong protein materials such as spider silk. This indicates the necessity of understanding fundamental principles providing insight into how amyloid fibrils exhibit the excellent mechanical properties, which may allow for developing biomimetic materials whose material (e.g., mechanical) properties can be controlled. Here, we describe recent efforts to characterize the nanomechanical properties of amyloid fibrils using computational simulations (e.g., atomistic simulations) and single-molecule experiments (e.g., atomic force microscopy experiments). This paper summarizes theoretical models, which are useful in analyzing the mechanical properties of amyloid fibrils based on simulations and experiments, such as continuum elastic (beam) model, elastic network model, and polymer statistical model. In this paper, we suggest how the nanomechanical properties of amyloid fibrils can be characterized and determined using computational simulations and/or atomic force microscopy experiments coupled with the theoretical models.

scholarly journals Single-molecular and Ensemble-level Oscillations of Cyanobacterial Circadian Clock

2018 ◽  
Author(s):  
Sumita Das ◽  
Tomoki P. Terada ◽  
Masaki Sasai
Keyword(s):  
Atpase Activity ◽  
Circadian Clock ◽  
Single Molecule ◽  
Structural Changes ◽  
Atp Hydrolysis ◽  
Theoretical Models ◽  
Oscillation Period ◽  
Coarse Grained ◽  
Simulation Results

AbstractWhen three cyanobacterial proteins, KaiA, KaiB, and KaiC, are incubated with ATP in vitro, the phosphorylation level of KaiC hexamers shows stable oscillation with approximately 24 h period. In order to understand this KaiABC clockwork, we need to analyze both the macroscopic synchronization of a large number of KaiC hexamers and the microscopic reactions and structural changes in individual KaiC molecules. In the present paper, we explain two coarse-grained theoretical models, the many-molecule (MM) model and the single-molecule (SM) model, to bridge the gap between macroscopic and microscopic understandings. In the simulation results with these models, ATP hydrolysis drives oscillation of individual KaiC hexamers and ATP hydrolysis is necessary for synchronizing oscillations of a large number of KaiC hexamers. Sensitive temperature dependence of the lifetime of the ADP bound state in the CI domain of KaiC hexamers makes the oscillation period temperature insensitive. ATPase activity is correlated to the frequency of phosphorylation oscillation in the single molecule of KaiC hexamer, which should be the origin of the observed ensemble-level correlation between the ATPase activity and the frequency of phosphorylation oscillation. Thus, the simulation results with the MM and SM models suggest that ATP hydrolysis randomly occurring in each CI domain of individual KaiC hexamers is a key process for oscillatory behaviors of the ensemble of many KaiC hexamers.Significance StatementCyanobacterial proteins, KaiA, KaiB, and KaiC, can reconstitute a circadian clock when they are incubated with ATP in vitro. In order to understand this prototypical oscillator, we need to analyze both synchronization of a macroscopically large number of oscillating molecules and microscopic reactions in individual molecules. We introduced two theoretical models to unify macroscopic and microscopic viewpoints. Simulation results suggest that ATP hydrolysis is necessary for synchronization and temperature compensation and that ATPase activity is correlated to the oscillation frequency in individual molecules. Thus, ATP hydrolysis randomly occurring in individual molecules should determine important features of the ensemble-level oscillation.

scholarly journals When Molecular Magnetism Meets Supramolecular Chemistry: Multifunctional and Multiresponsive Dicopper(II) Metallacyclophanes as Proof-of-Concept for Single-Molecule Spintronics and Quantum Computing Technologies?

2020 ◽  
Vol 6 (4) ◽  
pp. 69
Author(s):  
Renato Rabelo ◽  
Salah-Eddine Stiriba ◽  
Danielle Cangussu ◽  
Cynthia L. M. Pereira ◽  
Nicolás Moliner ◽  
...  
Keyword(s):  
Quantum Computing ◽  
Single Molecule ◽  
Quantum Coherence ◽  
Quantum Information Processing ◽  
Research Work ◽  
Theoretical Models ◽  
Magnetic Interactions ◽  
Molecular Magnetism ◽  
Special Focus ◽  
Dinuclear Metal Complexes

Molecular magnetism has made a long journey, from the fundamental studies on through-ligand electron exchange magnetic interactions in dinuclear metal complexes with extended organic bridges to the more recent exploration of their electron spin transport and quantum coherence properties. Such a field has witnessed a renaissance of dinuclear metallacyclic systems as new experimental and theoretical models for single-molecule spintronics and quantum computing, due to the intercrossing between molecular magnetism and metallosupramolecular chemistry. The present review reports a state-of-the-art overview as well as future perspectives on the use of oxamato-based dicopper(II) metallacyclophanes as promising candidates to make multifunctional and multiresponsive, single-molecule magnetic (nano)devices for the physical implementation of quantum information processing (QIP). They incorporate molecular magnetic couplers, transformers, and wires, controlling and facilitating the spin communication, as well as molecular magnetic rectifiers, transistors, and switches, exhibiting a bistable (ON/OFF) spin behavior under external stimuli (chemical, electronic, or photonic). Special focus is placed on the extensive research work done by Professor Francesc Lloret, an outstanding chemist, excellent teacher, best friend, and colleague, in recognition of his invaluable contributions to molecular magnetism on the occasion of his 65th birthday.

Out-migration and social capital

2021 ◽  
pp. 181-188
Author(s):  
Nicholas Spina
Keyword(s):  
Social Capital ◽  
Theoretical Models ◽  
Statistical Analyses ◽  
Structural Level ◽  
Multivariate Statistical Analyses ◽  
Generalized Trust ◽  
Multivariate Statistical ◽  
Migration Data ◽  
Per Capita

This chapter explores how out-migration weakens social capital in sending communities. Based on game theoretical models of cooperation, it is theorized that the rate of subnational out-migration acts as a structural-level cue and informs residents about the prospect of future interactions between citizens. Heavy out-migration creates a cooperative dilemma by provoking doubt among residents about the benefits of extending trust to and engaging with strangers who may not remain in the community. This proposition is tested using subnational migration data from Bulgaria in two multivariate statistical analyses. The finding from the first set of models confirms that citizens residing in regions undergoing more out-migration report lower levels of generalized trust. A second series of tests reveal that subnational regions with more out-migration have fewer associational memberships per capita.

scholarly journals Basic mechanisms and kinetics of pause-interspersed transcript elongation

2020 ◽  
Author(s):  
Jin Qian ◽  
David Dunlap ◽  
Laura Finzi
Keyword(s):  
Single Molecule ◽  
Regulation Of Gene Expression ◽  
Theoretical Models ◽  
Dna Templates ◽  
Basic Assumptions ◽  
Transcript Elongation ◽  
Single Molecule Studies ◽  
Transcriptional Pausing ◽  
Polymerase Pausing ◽  
Kinetics Of

Abstract RNA polymerase pausing during elongation is an important mechanism in the regulation of gene expression. Pausing along DNA templates is thought to be induced by distinct signals encoded in the nucleic acid sequence and halt elongation complexes to allow time for necessary co-transcriptional events. Pausing signals have been classified as those producing short-lived elemental, long-lived backtracked, or hairpin-stabilized pauses. In recent years, structural microbiology and single-molecule studies have significantly advanced our understanding of the paused states, but the dynamics of these states are still uncertain, although several models have been proposed to explain the experimentally observed pausing behaviors. This review summarizes present knowledge about the paused states, discusses key discrepancies among the kinetic models and their basic assumptions, and highlights the importance and challenges in constructing theoretical models that may further our biochemical understanding of transcriptional pausing.

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