Single-molecule biophysics experiments in silico: Toward a physical model of a replisome

Chou, Hong‐Nong; Aksimentiev, Aleksei

doi:10.1016/j.isci.2022.104264

Cited by 5 publications

(6 citation statements)

References 88 publications

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“…Such diffusion processes are often rate limiting to the overall energy conversion rate as is the case in the chromatophore. ,,, MD simulations are particularly suitable to address these intermediary time scales where charge migration can be addressed as a classical process; specifically, the spatial inhomogeneity of the photosynthetic domain can be taken into account in terms of its electrostatic influence on charge carrier mobility. However, diffusion time scales typically remain beyond the reach of brute force all-atom MD simulations and are instead addressed by MD-based coarse-grained protocols such as atomic resolution Brownian Dynamics (ARBD). , The resulting charge gradient generated across the membrane as a consequence of the aforementioned charge migration processes drives the synthesis of ATP (tens of milliseconds) at the ATP synthase, , culminating the conversion of solar energy into stable chemical bonds for later use.…”

Section: Resulting Applicationsmentioning

confidence: 99%

“…However, diffusion time scales typically remain beyond the reach of brute force all-atom MD simulations and are instead addressed by MD-based coarsegrained protocols such as atomic resolution Brownian Dynamics (ARBD). 185,186 The resulting charge gradient generated across the membrane as a consequence of the aforementioned charge migration processes drives the synthesis of ATP (tens of milliseconds) at the ATP synthase, 160,181 culminating the conversion of solar energy into stable chemical bonds for later use.…”

Section: Methodsmentioning

confidence: 99%

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Perspective on Integrative Simulations of Bioenergetic Domains

Pirnia,

Maqdisi,

Mittal

et al. 2024

J. Phys. Chem. B

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Bioenergetic processes in cells, such as photosynthesis or respiration, integrate many time and length scales, which makes the simulation of energy conversion with a mere single level of theory impossible. Just like the myriad of experimental techniques required to examine each level of organization, an array of overlapping computational techniques is necessary to model energy conversion. Here, a perspective is presented on recent efforts for modeling bioenergetic phenomena with a focus on molecular dynamics simulations and its variants as a primary method. An overview of the various classical, quantum mechanical, enhanced sampling, coarse-grained, Brownian dynamics, and Monte Carlo methods is presented. Example applications discussed include multiscale simulations of membrane-wide electron transport, rate kinetics of ATP turnover from electrochemical gradients, and finally, integrative modeling of the chromatophore, a photosynthetic pseudo-organelle.

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Section: Resulting Applicationsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Perspective on Integrative Simulations of Bioenergetic Domains

Pirnia,

Maqdisi,

Mittal

et al. 2024

J. Phys. Chem. B

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“…There is no sequence-specificity in the homopolymer model of replicating chromosomes beyond specific landmark monomers such as Ori s and Ter s, and there is no means to represent ssDNA. This limitation precludes us from modeling the unique molecular structures of the bubble during replication initation ( Shimizu et al, 2016 ) and replisome during replication ( Maffeo et al, 2022 ). The essentiality of HU in Syn3A despite its reduced proteomics count and high-affinity for structurally deformed DNA ( Kamashev, 2000 ) suggests a role in DNA replication, which is further supported by the Ori : Ter ratio of B. subtilis being reduced upon HU deletion ( Karaboja and Wang, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Dynamics of chromosome organization in a minimal bacterial cell

Gilbert

Thornburg

Brier

et al. 2023

Front. Cell Dev. Biol.

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Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics, we investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell-cycle. To achieve cell-scale chromosome structures that are realistic, we model the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A. In addition, the conformations of the circular DNA must avoid overlapping with ribosomes identitied in cryo-electron tomograms. While Syn3A lacks the complex regulatory systems known to orchestrate chromosome segregation in other bacteria, its minimized genome retains essential loop-extruding structural maintenance of chromosomes (SMC) protein complexes (SMC-scpAB) and topoisomerases. Through implementing the effects of these proteins in our simulations of replicating chromosomes, we find that they alone are sufficient for simultaneous chromosome segregation across all generations within nested theta structures. This supports previous studies suggesting loop-extrusion serves as a near-universal mechanism for chromosome organization within bacterial and eukaryotic cells. Furthermore, we analyze ribosome diffusion under the influence of the chromosome and calculate in silico chromosome contact maps that capture inter-daughter interactions. Finally, we present a methodology to map the polymer model of the chromosome to a Martini coarse-grained representation to prepare molecular dynamics models of entire Syn3A cells, which serves as an ultimate means of validation for cell states predicted by the WCM.

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“…However, diffusion timescales typically remain beyond the reach of brute force all-atom MD simulations and are instead addressed by MD-based coarse-grained protocols such as atomic resolution Brownian Dynamics (ARBD). 172,173 The resulting charge gradient generated across the membrane as a consequence of the aforementioned charge migration processes drives the synthesis of ATP (tens of milliseconds) at the ATP synthase, 146,167 culminating the conversion of solar energy into stable chemical bonds for later use.…”

Section: Atp Synthasementioning

confidence: 99%

Perspective on Integrative Simulations of Bioenergetic Domains

Pirnia,

Maqdisi,

Mital

et al. 2023

Preprint

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Bioenergetic processes in cells, such as photosynthesis or respiration, integrate so many time and length scales that they hinder the simulation of energy conversion with a mere single level of theory. Just like the myriad of experimental techniques required to examine each level of organization, an array of overlapping computational techniques is necessary to model energy conversion. Here, a perspective is presented on recent efforts for modeling bioenergetic phenomena with focus on molecular dynamics simulations and its variants as a primary method. An overview of the various classical, quantum mechanical, enhanced sampling, coarse-grained, Brownian dynamics, and Monte-Carlo methods is presented. Example applications discussed include multi- scale simulations of membrane-wide electron transport, rate kinetics of ATP turnover from electrochemical gradients and finally, integrative modeling of the chromatophore, a photosynthetic pseudo-organelle.

show abstract

Single-molecule biophysics experiments in silico: Toward a physical model of a replisome

Cited by 5 publications

References 88 publications

Perspective on Integrative Simulations of Bioenergetic Domains

Perspective on Integrative Simulations of Bioenergetic Domains

Dynamics of chromosome organization in a minimal bacterial cell

Perspective on Integrative Simulations of Bioenergetic Domains

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