scholarly journals Accurate sequence-dependent coarse-grained model for conformational and elastic properties of double-stranded DNA

2021 ◽  
Author(s):  
Salvatore Assenza ◽  
Rubén Pérez
Keyword(s):  
Persistence Length ◽  
Independent Set ◽  
Single Step ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Sequence Dependence ◽  
Cellular Processes ◽  
Coarse Grained Model ◽  
Double Stranded Dna ◽  
Sequence Dependent

AbstractWe introduce MADna, a sequence-dependent coarse-grained model of double-stranded DNA (dsDNA), where each nucleotide is described by three beads localized at the sugar and base moieties, and at the phosphate group. The sequence dependence is included by considering a step-dependent parameterization of the bonded interactions, which are tuned in order to reproduce the values of key observables obtained from exhaustive atomistic simulations from literature. The predictions of the model are benchmarked against an independent set of all-atom simulations, showing that it captures with high fidelity the sequence dependence of conformational and elastic features beyond the single step considered in its formulation. A remarkably good agreement with experiments is found for both sequence-averaged and sequence-dependent conformational and elastic features, including the stretching and torsion moduli, the twist-stretch and twist-bend couplings, the persistence length and the helical pitch. Overall, for the inspected quantities, the model has a precision comparable to atomistic simulations, hence providing a reliable coarse-grained description for the rationalization of singlemolecule experiments and the study of cellular processes involving dsDNA. Owing to the simplicity of its formulation, MADna can be straightforwardly included in common simulation engines.

scholarly journals Sequence-dependent Three Interaction Site (TIS) Model for Single and Double-stranded DNA

2018 ◽  
Author(s):  
Debayan Chakraborty ◽  
Naoto Hori ◽  
D. Thirumalai
Keyword(s):  
Electrostatic Interactions ◽  
Persistence Length ◽  
Data Bank ◽  
Coarse Grained ◽  
Force Extension ◽  
Sequence Dependence ◽  
Coarse Grained Model ◽  
Interaction Sites ◽  
Double Stranded Dna ◽  
Centers Of Mass

AbstractWe develop a robust coarse-grained model for single and double stranded DNA by representing each nucleotide by three interaction sites (TIS) located at the centers of mass of sugar, phosphate, and base. The resulting TIS model includes base-stacking, hydrogen bond, and electrostatic interactions as well as bond-stretching and bond angle potentials that account for the polymeric nature of DNA. The choices of force constants for stretching and the bending potentials were guided by a Boltzmann inversion procedure using a large representative set of DNA structures extracted from the Protein Data Bank. Some of the parameters in the stacking interactions were calculated using a learning procedure, which ensured that the experimentally measured melting temperatures of dimers are faithfully reproduced. Without any further adjustments, the calculations based on the TIS model reproduces the experimentally measured salt and sequence dependence of the size of single stranded DNA (ssDNA), as well as the persistence lengths of poly(dA) and poly(dT) chains. Interestingly, upon application of mechanical force the extension of poly(dA) exhibits a plateau, which we trace to the formation of stacked helical domains. In contrast, the force-extension curve (FEC) of poly(dT) is entropic in origin, and could be described by a standard polymer model. We also show that the persistence length of double stranded DNA, formed from two complementary ssDNAs with one hundred and thirty base pairs, is consistent with the prediction based on the worm-like chain. The persistence length, which decreases with increasing salt concentration, is in accord with the Odijk-Skolnick-Fixman theory intended for stiff polyelectrolyte chains near the rod limit. The range of applications, which did not require adjusting any parameter after the initial construction based solely on PDB structures and melting profiles of dimers, attests to the transferability and robustness of the TIS model for ssDNA and dsDNA.

scholarly journals A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion

2020 ◽  
Author(s):  
Alvin Yu ◽  
Alexander J. Pak ◽  
Peng He ◽  
Viviana Monje-Galvan ◽  
Lorenzo Casalino ◽  
...  
Keyword(s):  
Large Scale ◽  
Molecular Model ◽  
Structural Data ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Current Status ◽  
Multiscale Approach ◽  
X Ray Crystallography ◽  
Coarse Grained Model ◽  
Viral Particles

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Computer simulations of complete viral particles can provide theoretical insights into large-scale viral processes including assembly, budding, egress, entry, and fusion. Detailed atomistic simulations, however, are constrained to shorter timescales and require billion-atom simulations for these processes. Here, we report the current status and on-going development of a largely “bottom-up” coarse-grained (CG) model of the SARS-CoV-2 virion. Structural data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion model. We describe how CG molecular interactions can be derived from all-atom simulations, how viral behavior difficult to capture in atomistic simulations can be incorporated into the CG models, and how the CG models can be iteratively improved as new data becomes publicly available. Our initial CG model and the detailed methods presented are intended to serve as a resource for researchers working on COVID-19 who are interested in performing multiscale simulations of the SARS-CoV-2 virion.Significance StatementThis study reports the construction of a molecular model for the SARS-CoV-2 virion and details our multiscale approach towards model refinement. The resulting model and methods can be applied to and enable the simulation of SARS-CoV-2 virions.

scholarly journals Single-molecule biophysics experiments in silico: Towards a physical model of a replisome

2021 ◽  
Author(s):  
Christopher Maffeo ◽  
Han-Yi Chou ◽  
Aleksei Aksimentiev
Keyword(s):  
Single Molecule ◽  
In Silico ◽  
Computational Models ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Test Bed ◽  
Computing Power ◽  
Coarse Grained Model ◽  
Biomolecular Dynamics ◽  
Single Molecule Studies

AbstractThe interpretation of single-molecule experiments is frequently aided by computational modeling of biomolecular dynamics. The growth of computing power and ongoing validation of computational models suggest that it soon may be possible to replace some experiments out-right with computational mimics. Here we offer a blueprint for performing single-molecule studies in silico using a DNA binding protein as a test bed. We demonstrate how atomistic simulations, typically limited to sub-millisecond durations and zeptoliter volumes, can guide development of a coarse-grained model for use in simulations that mimic experimental assays. We show that, after initially correcting excess attraction between the DNA and protein, qualitative consistency between several experiments and their computational equivalents is achieved, while additionally providing a detailed portrait of the underlying mechanics. Finally the model is used to simulate the trombone loop of a replication fork, a large complex of proteins and DNA.

Developing Coarse-Grained Force Fields of Poly (methylmethacrylate-b-2-vinylpyridine) from Atomistic Simulation

2012 ◽  
Vol 562-564 ◽  
pp. 123-128 ◽  
Author(s):  
Bo Du ◽  
Zi Lu Wang ◽  
Xue Hao He
Keyword(s):  
Mechanical Properties ◽  
Force Field ◽  
Self Assembly ◽  
Atomistic Simulation ◽  
Polymer Melts ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Inversion Method ◽  
Coarse Grained Model ◽  
Vinyl Pyridine

A coarse-grained force field for poly (methylmethacrylate-b-2-vinyl pyridine) is developed based on the Iterative Boltzmann Inversion method. The proposed coarse-grained model, successfully reproduced the properties of the polymer melts obtained from atomistic simulations, may provide an efficient way to study their mechanical properties and self-assembly behaviors.

scholarly journals On the Importance of Hydrodynamic Interactions in the Stepping Kinetics of Kinesin

2016 ◽  
Author(s):  
Dave Thirumalai ◽  
Yonathan Goldtzvik ◽  
Zhechun Zhang
Keyword(s):  
Coiled Coil ◽  
Quantitative Agreement ◽  
Single Step ◽  
Hydrodynamic Interactions ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Target Binding ◽  
Conventional Kinesin ◽  
Kinetics Of ◽  
Target Binding Site

Conventional kinesin walks by a hand-over-hand mechanism on the microtubule (MT) by taking ∼ 8nmdiscrete steps, and consumes one ATP molecule per step. The time needed to complete a single step is on the order of twenty microseconds. We show, using simulations of a coarse-grained model of the complex containing the two motor heads, the MT, and the coiled coil that in order to obtain quantitative agreement with experiments for the stepping kinetics hydrodynamic interactions (HI) have to be included. In simulations without hydrodynamic interactions spanning nearly twenty microseconds not a single step was completed in hundred trajectories. In sharp contrast, nearly 14% of the steps reached the target binding site within 6 microseconds when HI were included. Somewhat surprisingly, there are qualitative differences in the diffusion pathways in simulations with and without HI. The extent of movement of the trailing head of kinesin on the MT during the diffusion stage of stepping is considerably greater in simulations with HI than in those without HI. Our results suggest that inclusion of HI is crucial in the accurate description of motility of other motors as well.

Coarse-Grained Model for Sequence-Dependent Adsorption of ssDNA on Carbon Nanotubes

2014 ◽  
Vol 118 (31) ◽  
pp. 17677-17685 ◽  
Author(s):  
Olga Kucher ◽  
Irena Yungerman ◽  
Simcha Srebnik
Keyword(s):  
Carbon Nanotubes ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Sequence Dependent

scholarly journals Development of Coarse-Grained Models for Poly(4-vinylphenol) and Poly(2-vinylpyridine): Polymer Chemistries with Hydrogen Bonding

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2764
Author(s):  
Utkarsh Kapoor ◽  
Arjita Kulshreshtha ◽  
Arthi Jayaraman
Keyword(s):  
Hydrogen Bonding ◽  
Bond Angle ◽  
Persistence Length ◽  
Distance Distribution ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Implicit Solvent ◽  
End Distance ◽  
End To End ◽  
Chain Lengths

In this paper, we identify the modifications needed in a recently developed generic coarse-grained (CG) model that captured directional interactions in polymers to specifically represent two exemplary hydrogen bonding polymer chemistries—poly(4-vinylphenol) and poly(2-vinylpyridine). We use atomistically observed monomer-level structures (e.g., bond, angle and torsion distribution) and chain structures (e.g., end-to-end distance distribution and persistence length) of poly(4-vinylphenol) and poly(2-vinylpyridine) in an explicitly represented good solvent (tetrahydrofuran) to identify the appropriate modifications in the generic CG model in implicit solvent. For both chemistries, the modified CG model is developed based on atomistic simulations of a single 24-mer chain. This modified CG model is then used to simulate longer (36-mer) and shorter (18-mer and 12-mer) chain lengths and compared against the corresponding atomistic simulation results. We find that with one to two simple modifications (e.g., incorporating intra-chain attraction, torsional constraint) to the generic CG model, we are able to reproduce atomistically observed bond, angle and torsion distributions, persistence length, and end-to-end distance distribution for chain lengths ranging from 12 to 36 monomers. We also show that this modified CG model, meant to reproduce atomistic structure, does not reproduce atomistically observed chain relaxation and hydrogen bond dynamics, as expected. Simulations with the modified CG model have significantly faster chain relaxation than atomistic simulations and slower decorrelation of formed hydrogen bonds than in atomistic simulations, with no apparent dependence on chain length.

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