Assessment of the DNA Partial Specific Volume and Hydration Layer Properties from the CHARMM Drude Polarizable and Additive MD Simulations

2021 ◽  
Author(s):  
Alexey Savelyev
Keyword(s):  
Molecular Dynamics ◽  
Specific Volume ◽  
Md Simulations ◽  
Partial Specific Volume ◽  
Hydration Layer ◽  
Accurate Computation ◽  
Explicit Solvent

In this study we report on the accurate computation of the biomolecular partial specific volume (PSV) from explicit-solvent molecular dynamics (MD) simulations. The case of the DNA is considered, and...

scholarly journals Aβ Fibrils Can Act as Aqueous Pores: a Molecular Dynamics Study

2018 ◽  
Author(s):  
S. Natesh ◽  
J. R. Sachleben ◽  
T. R Sosnick ◽  
K. F. Freed ◽  
S. C. Meredith ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Rotational Symmetry ◽  
Md Simulations ◽  
Salt Bridges ◽  
Nmr Studies ◽  
Explicit Solvent ◽  
Hydrogen Deuterium ◽  
A Cell ◽  
Aβ Fibrils ◽  
Bidirectional Flow

AbstractAggregation of Aβ peptides is important in the etiology of Alzheimer’s Disease (AD), an increasingly prevalent neurodegenerative disease. We ran multiple ∼ 300 ns all-atom explicit solvent molecular dynamics (MD) simulations starting from three NMR-based structural models of Aβ(1-40 residues) fibrils having 2-fold (pdb code 2LMN) or 3-fold rotational symmetry (2LMP, and 2M4J). The 2M4J structure is based on an AD brain-seeded fibril whereas 2LMP and 2LMN represent two all-synthetic fibrils. Fibrils are constructed to contain either 6 or an infinite number of layers made using periodic images. The 6 layer fibrils partially unravel over the simulation time, mainly at their ends, while infinitely long fibrils do not. Once formed, the D23-K28 salt bridges are very stable and form within and between chains. Fibrils tend to retain (2LMN and 2LMP) or develop (2M4J) a “stagger” or register shift of β-strands along the fibril axis. The brain-seeded fibril rapidly develops gaps at the sides of the fibril, which allows bidirectional flow of water and ions from the bulk phase in and out the central longitudinal core of the fibril. Similar but less marked changes were also observed for the 2LMP fibrils. The residues defining the gaps largely coincide with those demonstrated to have relatively rapid Hydrogen-Deuterium exchange in solid state NMR studies. These observations suggest that Aβ(1-40 residues) fibrils may act as aqueous pores that might disrupt water and ion fluxes if inserted into a cell membrane.

scholarly journals Ab Initio Molecular Dynamics Simulations to Interpret the Molecular Fragmentation Induced in Deoxyribose by Synchrotron Soft X-Rays

2019 ◽  
Vol 3 (4) ◽  
pp. 24
Author(s):  
Marie-Anne Hervé du Penhoat ◽  
Anis Hamila ◽  
Marie-Pierre Gaigeot ◽  
Rodolphe Vuilleumier ◽  
Kentaro Fujii ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Ab Initio ◽  
Density Functional ◽  
Md Simulations ◽  
Ab Initio Molecular Dynamics ◽  
X Rays ◽  
Auger Decay ◽  
Hydration Layer ◽  
The Core ◽  
Dynamics Simulations

It has been suggested that core ionization in DNA atoms could induce complex, irreparable damage. Synchrotron soft X-rays have been used to probe the damage induced by such events in thin films of DNA components. In a complementary approach, we investigate the fragmentation dynamics following a carbon or oxygen K-shell ionization in 2-deoxy-D-ribose (DR), a major component in the DNA chain. Core ionization of the sugars hydration layer is also studied. To that aim, we use state-of-the-art ab initio Density Functional Theory-based Molecular Dynamics (MD) simulations. The ultrafast dissociation dynamics of the core ionized molecule, prior Auger decay, is modeled for about 10 fs. We show that the core-ionization of oxygen atoms within DR or its hydration layer may induce proton transfers towards nearby molecules, before Auger decay. In a second step, we model an Auger effect occurring either at the beginning or at the end of the core–hole dynamics. Two electrons are removed from the deepest valence molecular orbitals localized on the initially core-ionized oxygen atom (O*), and this electronic state is propagated by means of Ehrenfest MD. We show an ultrafast dissociation of the DR2+ molecule C-O* bonds, which, in most cases, seems independent of the time at which Auger decay occurs.

scholarly journals Development of transferable coarse-grained models of amino acids

2020 ◽  
Vol 5 (3) ◽  
pp. 675-685 ◽  
Author(s):  
Olivia Conway ◽  
Yaxin An ◽  
Karteek K. Bejagam ◽  
Sanket A. Deshmukh
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Md Simulations ◽  
Peptide Amphiphiles ◽  
Coarse Grained ◽  
Explicit Solvent

We have developed transferable coarse-grained (CG) models of the twenty standard amino acids, which can be used to perform molecular dynamics (MD) simulations of peptide amphiphiles (PAs) in the presence of explicit solvent.

Binding modes and pathway of RHPS4 to human telomeric G-quadruplex and duplex DNA probed by all-atom molecular dynamics simulations with explicit solvent

2017 ◽  
Vol 19 (28) ◽  
pp. 18685-18694 ◽  
Author(s):  
Kelly Mulholland ◽  
Farzana Siddiquei ◽  
Chun Wu
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Md Simulations ◽  
Duplex Dna ◽  
Binding Modes ◽  
Dna Duplex ◽  
Explicit Solvent ◽  
G Quadruplex ◽  
Dynamics Simulations

Binding modes ofRHPS4to DNA duplex and human teloemeric G-quadruplexes from MD simulations.

Efficient Treatment of Fixed and Induced Dipolar Interactions

2000 ◽  
Vol 653 ◽  
Author(s):  
Celeste Sagui ◽  
Thoma Darden
Keyword(s):  
Molecular Dynamics ◽  
Md Simulations ◽  
Lagrangian Formalism ◽  
Dipolar Interactions ◽  
Time Step ◽  
Efficient Treatment ◽  
Particle Mesh Ewald ◽  
Fixed Charges ◽  
Self Consistency ◽  
Induced Dipoles

AbstractFixed and induced point dipoles have been implemented in the Ewald and Particle-Mesh Ewald (PME) formalisms. During molecular dynamics (MD) the induced dipoles can be propagated along with the atomic positions either by interation to self-consistency at each time step, or by a Car-Parrinello (CP) technique using an extended Lagrangian formalism. The use of PME for electrostatics of fixed charges and induced dipoles together with a CP treatment of dipole propagation in MD simulations leads to a cost overhead of only 33% above that of MD simulations using standard PME with fixed charges, allowing the study of polarizability in largemacromolecular systems.

Split the Charge Difference in Two! a Rule of Thumb for Adding Proper Amounts of Ions in MD Simulations

2020 ◽  
Author(s):  
Matías R. Machado ◽  
Sergio Pantano
Keyword(s):  
Molecular Dynamics ◽  
Ionic Strength ◽  
Molecular Simulations ◽  
Md Simulations ◽  
Good Practices ◽  
Rule Of Thumb ◽  
Ionic Concentrations

<p> Despite the relevance of properly setting ionic concentrations in Molecular Dynamics (MD) simulations, methods or practical rules to set ionic strength are scarce and rarely documented. Based on a recently proposed thermodynamics method we provide an accurate rule of thumb to define the electrolytic content in simulation boxes. Extending the use of good practices in setting up MD systems is promptly needed to ensure reproducibility and consistency in molecular simulations.</p>

Assessing the Antimalarial Potentials of Phytochemicals: Virtual Screening, Molecular Dynamics and In-Vitro Investigations

2019 ◽  
Vol 16 (3) ◽  
pp. 291-300
Author(s):  
Saumya K. Patel ◽  
Mohd Athar ◽  
Prakash C. Jha ◽  
Vijay M. Khedkar ◽  
Yogesh Jasrai ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Structural Integrity ◽  
Md Simulations ◽  
Tylophora Indica ◽  
Multidrug Resistance Protein 1 ◽  
Receptor Complexes ◽  
Resistance Protein ◽  
Dynamics Simulations ◽  
Stable Trajectory

Background: Combined in-silico and in-vitro approaches were adopted to investigate the antiplasmodial activity of Catharanthus roseus and Tylophora indica plant extracts as well as their isolated components (vinblastine, vincristine and tylophorine). </P><P> Methods: We employed molecular docking to prioritize phytochemicals from a library of 26 compounds against Plasmodium falciparum multidrug-resistance protein 1 (PfMDR1). Furthermore, Molecular Dynamics (MD) simulations were performed for a duration of 10 ns to estimate the dynamical structural integrity of ligand-receptor complexes. </P><P> Results: The retrieved bioactive compounds viz. tylophorine, vinblastin and vincristine were found to exhibit significant interacting behaviour; as validated by in-vitro studies on chloroquine sensitive (3D7) as well as chloroquine resistant (RKL9) strain. Moreover, they also displayed stable trajectory (RMSD, RMSF) and molecular properties with consistent interaction profile in molecular dynamics simulations. </P><P> Conclusion: We anticipate that the retrieved phytochemicals can serve as the potential hits and presented findings would be helpful for the designing of malarial therapeutics.

scholarly journals On the Use of the Discrete Constant pH Molecular Dynamics to Describe the Conformational Space of Peptides

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 99
Author(s):  
Cristian Privat ◽  
Sergio Madurga ◽  
Francesc Mas ◽  
Jaime Rubio-Martínez
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Md Simulations ◽  
Point Of View ◽  
Conformational Space ◽  
Conformational Sampling ◽  
Protonation State ◽  
Constant Ph ◽  
Biochemical Systems ◽  
Constant Ph Molecular Dynamics

Solvent pH is an important property that defines the protonation state of the amino acids and, therefore, modulates the interactions and the conformational space of the biochemical systems. Generally, this thermodynamic variable is poorly considered in Molecular Dynamics (MD) simulations. Fortunately, this lack has been overcome by means of the Constant pH Molecular Dynamics (CPHMD) methods in the recent decades. Several studies have reported promising results from these approaches that include pH in simulations but focus on the prediction of the effective pKa of the amino acids. In this work, we want to shed some light on the CPHMD method and its implementation in the AMBER suitcase from a conformational point of view. To achieve this goal, we performed CPHMD and conventional MD (CMD) simulations of six protonatable amino acids in a blocked tripeptide structure to compare the conformational sampling and energy distributions of both methods. The results reveal strengths and weaknesses of the CPHMD method in the implementation of AMBER18 version. The change of the protonation state according to the chemical environment is presumably an improvement in the accuracy of the simulations. However, the simulations of the deprotonated forms are not consistent, which is related to an inaccurate assignment of the partial charges of the backbone atoms in the CPHMD residues. Therefore, we recommend the CPHMD methods of AMBER program but pointing out the need to compare structural properties with experimental data to bring reliability to the conformational sampling of the simulations.

scholarly journals Unveiling Carbon Dioxide and Ethanol Diffusion in Carbonated Water-Ethanol Mixtures by Molecular Dynamics Simulations

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1711
Author(s):  
Mohamed Ahmed Khaireh ◽  
Marie Angot ◽  
Clara Cilindre ◽  
Gérard Liger-Belair ◽  
David A. Bonhommeau
Keyword(s):  
Carbon Dioxide ◽  
Molecular Dynamics ◽  
Diffusion Coefficients ◽  
Hydrodynamic Radius ◽  
Md Simulations ◽  
Molecular Models ◽  
Experimental Values ◽  
Carbon Dioxide Co2 ◽  
Dynamics Simulations ◽  
Apparent Disagreement

The diffusion of carbon dioxide (CO2) and ethanol (EtOH) is a fundamental transport process behind the formation and growth of CO2 bubbles in sparkling beverages and the release of organoleptic compounds at the liquid free surface. In the present study, CO2 and EtOH diffusion coefficients are computed from molecular dynamics (MD) simulations and compared with experimental values derived from the Stokes-Einstein (SE) relation on the basis of viscometry experiments and hydrodynamic radii deduced from former nuclear magnetic resonance (NMR) measurements. These diffusion coefficients steadily increase with temperature and decrease as the concentration of ethanol rises. The agreement between theory and experiment is suitable for CO2. Theoretical EtOH diffusion coefficients tend to overestimate slightly experimental values, although the agreement can be improved by changing the hydrodynamic radius used to evaluate experimental diffusion coefficients. This apparent disagreement should not rely on limitations of the MD simulations nor on the approximations made to evaluate theoretical diffusion coefficients. Improvement of the molecular models, as well as additional NMR measurements on sparkling beverages at several temperatures and ethanol concentrations, would help solve this issue.

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