Rings, Hexagons, Petals, and Dipolar Moment Sink-Sources: The Fanciful Behavior of Water around Cyclodextrin Complexes

The basket-like geometry of cyclodextrins (CDs), with a cavity able to host hydrophobic groups, makes these molecules well suited for a large number of fundamental and industrial applications. Most of the established CD-based applications rely on trial and error studies, often ignoring key information at the atomic level that could be employed to design new products and to optimize their use. Computational simulations are well suited to fill this gap, especially in the case of CD systems due to their low number of degrees of freedom compared with typical macromolecular systems. Thus, the design and validation of solid and efficient methods to simulate and analyze CD-based systems is key to contribute to this field. The behavior of supramolecular complexes critically depends on the media where they are embedded, so the detailed characterization of the solvent is required to fully understand these systems. In the present work, we use the inclusion complex formed by two α-CDs and one sodium dodecyl sulfate molecule to test eight different parameterizations of the GROMOS and AMBER force fields, including several methods aimed to increase the conformational sampling in computational molecular dynamics simulation trajectories. The system proved to be extremely sensitive to the employed force field, as well as to the presence of a water/air interface. In agreement with previous experiments and in contrast to the results obtained with AMBER, the analysis of the simulations using GROMOS showed a quick adsorption of the complex to the interface as well as an extremely exotic behavior of the water molecules surrounding the structure both in the bulk aqueous solution and at the water surface. The chirality of the CD molecule seems to play an important role in this behavior. All together, these results are expected to be useful to better understand the behavior of CD-based supramolecular complexes such as adsorption or aggregation driving forces, as well as to introduce new methods able to speed up general MD simulations.

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Manuscript-C-dots assembly at interface-041020.pdf

10.26434/chemrxiv.12114063 ◽

2020 ◽

Author(s):

Amin Reza Zolghadr ◽

Behnam Rostami

Keyword(s):

Self Assembly ◽

Carbon Dots ◽

Sodium Dodecyl ◽

Surface Region ◽

Systematic Investigation ◽

Dynamics Simulation ◽

Surface Tension Gradient ◽

Bivariate Analysis ◽

Air Interface ◽

Sds Surfactant

We describe a systematic investigation of carbon dots (C-dots) assemblies fabricated at the liquid/air interface because of the surface tension gradient. This gradient is originally created by capillary action and increased by addition of sodium dodecyl sulfate (SDS) surfactant or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) phospholipid to the surface of C-dots aqueous mixture. The arrangement of carbon dots in liquid bulk phase (before self-assembly) and at the surface region (after self-assembly) was examined by TEM microscopy. The presence of SDS surfactant and POPC phospholipid at the air/water interface induced the C-dots compression. In addition, molecular dynamics simulation was conducted to obtain the structure of C-dots at liquid/vapor interface. The orientation of C-dots is evaluated quantitatively at water/vapor surface by using bivariate analysis.

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Manuscript-C-dots assembly at interface-041020.pdf

10.26434/chemrxiv.12114063.v1 ◽

2020 ◽

Author(s):

Amin Reza Zolghadr ◽

Behnam Rostami

Keyword(s):

Self Assembly ◽

Carbon Dots ◽

Sodium Dodecyl ◽

Surface Region ◽

Systematic Investigation ◽

Dynamics Simulation ◽

Surface Tension Gradient ◽

Bivariate Analysis ◽

Air Interface ◽

Sds Surfactant

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A MOLECULAR DYNAMICS SIMULATION STUDY OF CONFORMATIONAL CHANGES AND SOLVATION OF Aβ PEPTIDE IN TRIFLUOROETHANOL AND WATER

Journal of Theoretical and Computational Chemistry ◽

10.1142/s0219633609004769 ◽

2009 ◽

Vol 08 (02) ◽

pp. 215-231 ◽

Cited By ~ 15

Author(s):

S. JALILI ◽

M. AKHAVAN

Keyword(s):

Molecular Dynamics ◽

Secondary Structure ◽

Conformational Changes ◽

Pure Water ◽

Sodium Dodecyl ◽

Md Simulations ◽

Dynamics Simulation ◽

Amyloid Beta Peptide ◽

Sodium Dodecyl Sulfate Micelle ◽

Beta Peptide

Molecular dynamics (MD) simulations of amyloid beta peptide have been performed in aqueous solutions of trifluoroethanol with different concentrations. The amount of α-helical secondary structure increases when going from pure water to trifluoroethanol-rich solutions. The conformation obtained in 40% (v/v) trifluoroethanol solution is very similar to the experimental observations of beta peptide in sodium dodecyl sulfate micelle. In this solution, the peptide has two helical segments connected through a looped region. The C-terminal helix of beta peptide unfolds in pure water. The effect of trifluoroethanol on peptide's secondary structure has been explained using the properties calculated from MD trajectories.

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Reversibly Sampling Conformations and Binding Modes Using Molecular Darting

10.26434/chemrxiv.12670676.v2 ◽

2020 ◽

Author(s):

Samuel C. Gill ◽

David Mobley

Keyword(s):

Monte Carlo ◽

Ligand Binding ◽

Binding Sites ◽

Degrees Of Freedom ◽

Dynamics Simulation ◽

Hiv Integrase ◽

Binding Modes ◽

System A ◽

Multiple Binding ◽

Internal Degrees Of Freedom

<div>Sampling multiple binding modes of a ligand in a single molecular dynamics simulation is difficult. A given ligand may have many internal degrees of freedom, along with many different ways it might orient itself a binding site or across several binding sites, all of which might be separated by large energy barriers. We have developed a novel Monte Carlo move called Molecular Darting (MolDarting) to reversibly sample between predefined binding modes of a ligand. Here, we couple this with nonequilibrium candidate Monte Carlo (NCMC) to improve acceptance of moves.</div><div>We apply this technique to a simple dipeptide system, a ligand binding to T4 Lysozyme L99A, and ligand binding to HIV integrase in order to test this new method. We observe significant increases in acceptance compared to uniformly sampling the internal, and rotational/translational degrees of freedom in these systems.</div>

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Recent Advances of In-Silico Modeling of Potent Antagonists for the Adenosine Receptors

Current Pharmaceutical Design ◽

10.2174/1381612825666190304123545 ◽

2019 ◽

Vol 25 (7) ◽

pp. 750-773 ◽

Cited By ~ 11

Author(s):

Pabitra Narayan Samanta ◽

Supratik Kar ◽

Jerzy Leszczynski

Keyword(s):

Drug Targets ◽

Biological Activities ◽

Scoring Function ◽

Md Simulations ◽

Energy Calculation ◽

Binding Modes ◽

Macromolecular Systems ◽

In Silico Modeling ◽

Mathematical Algorithms ◽

The Impact

The rapid advancement of computer architectures and development of mathematical algorithms offer a unique opportunity to leverage the simulation of macromolecular systems at physiologically relevant timescales. Herein, we discuss the impact of diverse structure-based and ligand-based molecular modeling techniques in designing potent and selective antagonists against each adenosine receptor (AR) subtype that constitutes multitude of drug targets. The efficiency and robustness of high-throughput empirical scoring function-based approaches for hit discovery and lead optimization in the AR family are assessed with the help of illustrative examples that have led to nanomolar to sub-micromolar inhibition activities. Recent progress in computer-aided drug discovery through homology modeling, quantitative structure-activity relation, pharmacophore models, and molecular docking coupled with more accurate free energy calculation methods are reported and critically analyzed within the framework of structure-based virtual screening of AR antagonists. Later, the potency and applicability of integrated molecular dynamics (MD) methods are addressed in the context of diligent inspection of intricated AR-antagonist binding processes. MD simulations are exposed to be competent for studying the role of the membrane as well as the receptor flexibility toward the precise evaluation of the biological activities of antagonistbound AR complexes such as ligand binding modes, inhibition affinity, and associated thermodynamic and kinetic parameters.

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

Polymers ◽

10.3390/polym13010099 ◽

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.

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A highly thermotolerant laccase produced by Cerrena unicolor strain CGMCC 5.1011 for complete and stable malachite green decolorization

AMB Express ◽

10.1186/s13568-020-01118-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yanhua Yao ◽

Guimei Zhou ◽

Yonghui Lin ◽

Xinqi Xu ◽

Jie Yang

Keyword(s):

Malachite Green ◽

Fermentation Broth ◽

Nitrogen Sources ◽

Life Time ◽

Industrial Applications ◽

Dynamics Simulation ◽

Carbon And Nitrogen ◽

Cdna Sequences ◽

Cerrena Unicolor ◽

Future Work

Abstract Laccases are a class of multi-copper oxidases with important industrial values. A thermotolerant laccase produced by a basidiomycete fungal strain Cerrena unicolor CGMCC 5.1011 was studied. With glycerin and peptone as the carbon and nitrogen sources, respectively, a maximal laccase activity of 121.7 U/mL was attained after cultivation in the shaking flask for 15 days. Transcriptomics analysis revealed an expressed laccase gene family of 12 members in C. unicolor strain CGMCC 5.1011, and the gene and cDNA sequences were cloned. A glycosylated laccase was purified from the fermentation broth of Cerrena unicolor CGMCC 5.1011 and corresponded to Lac2 based on MALDI-TOF MS/MS identification. Lac2 was stable at pH 5.0 and above, and was resistant to organic solvents. Lac2 displayed remarkable thermostability, with half-life time of 1.67 h at 70 ºC. Consistently, Lac2 was able to completely decolorize malachite green (MG) at high temperatures, whereas Lac7 from Cerrena sp. HYB07 resulted in accumulation of colored MG transformation intermediates. Molecular dynamics simulation of Lac2 was conducted, and possible mechanisms underlying Lac2 thermostability were discussed. The robustness of C. unicolor CGMCC 5.1011 laccase would not only be useful for industrial applications, but also provide a template for future work to develop thermostable laccases.

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Understanding Covalent Grafting of Nanotubes onto Polymer Nanocomposites: Molecular Dynamics Simulation Study

Sensors ◽

10.3390/s21082621 ◽

2021 ◽

Vol 21 (8) ◽

pp. 2621

Author(s):

Seunghwa Yang

Keyword(s):

Molecular Dynamics ◽

Load Transfer ◽

Cell Model ◽

Md Simulations ◽

Dynamics Simulation ◽

Covalent Grafting ◽

Modelling Strategies ◽

Multi Walled Carbon Nanotubes ◽

Walled Carbon Nanotubes ◽

External Loads

Here, we systematically interrogate the effects of grafting single-walled (SWNT) and multi-walled carbon nanotubes (MWNT) to polymer matrices by using molecular dynamics (MD) simulations. We specifically investigate key material properties that include interfacial load transfer, alteration of nanotube properties, and dispersion of nanotubes in the polymer matrix. Simulations are conducted on a periodic unit cell model of the nanocomposite with a straight carbon nanotube and an amorphous polyethylene terephthalate (PET) matrix. For each type of nanotube, either 0%, 1.55%, or 3.1% of the carbon atoms in the outermost nanotubes are covalently grafted onto the carbon atoms of the PET matrix. Stress-strain curves and the elastic moduli of nanotubes and nanocomposites are determined based on the density of covalent grafting. Covalent grafting promotes two rivalling effects with respect to altering nanotube properties, and improvements in interfacial load transfer in the nanocomposites are clearly observed. The enhanced interface enables external loads applied to the nanocomposites to be efficiently transferred to the grafted nanotubes. Covalent functionalization of the nanotube surface with PET molecules can alter the solubility of nanotubes and improve dispersibility. Finally, we discuss the current limitations and challenges in using molecular modelling strategies to accurately predict properties on the nanotube and polymers systems studied here.

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Fibers Effects on Contract Turbulence Using a Coupling Euler Model

Applied Sciences ◽

10.3390/app11157126 ◽

2021 ◽

Vol 11 (15) ◽

pp. 7126

Author(s):

Wei Yang ◽

Pei Hu

Keyword(s):

Boundary Layer ◽

Velocity Profile ◽

Fiber Orientation ◽

Bottom Layer ◽

Orientation Distribution ◽

Industrial Applications ◽

Dynamics Simulation ◽

Fiber Concentration ◽

Fibers Orientation ◽

Process Strategy

Fiber additive will induce the rheological behavior of suspension, resulting in variation in velocity profile and fiber orientation especially for the non-dilute case. Based on the fluid-solid coupling dynamics simulation, it shows that the fiber orientation aligns along the streamline more and more quickly in the central turbulent region as the fiber concentration increases, especially contract ratio Cx > 4. However, fibers tend to maintain the original uniform orientation and are rarely affected by the contract ratio in the boundary layer. The fibers orientation in the near semi-dilute phase is lower than that in the dilute phase near the outlet, which may be the result of the hydrodynamic contact lubrication between fibers. The orientation distribution and concentration of the fibers change the viscous flow mechanism of the suspension microscopically, which makes a velocity profile vary with the phase concentration. The velocity profile of the approaching semi-dilute phase sublayer is higher than that of the dilute and semi-dilute phases on the central streamline and in the viscous bottom layer, showing weak drag reduction while the situation is opposite on the logarithmic layer of the boundary layer. The relevant research can provide a process strategy for fiber orientation optimization and rheological control in the industrial applications of suspension.

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A Study on the Uniaxial Tension of FCC Metals at Nano Level Using MD

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.32.255 ◽

2008 ◽

Vol 32 ◽

pp. 255-258

Author(s):

Bohayra Mortazavi ◽

Akbar Afaghi Khatibi

Keyword(s):

Molecular Dynamics ◽

Uniaxial Tension ◽

Md Simulations ◽

Dynamics Simulation ◽

Face Centered Cubic ◽

Engineering Strain ◽

Fcc Metals ◽

Engineering Stress ◽

Nano Science ◽

Face Centered

Molecular Dynamics (MD) are now having orthodox means for simulation of matter in nano-scale. It can be regarded as an accurate alternative for experimental work in nano-science. In this paper, Molecular Dynamics simulation of uniaxial tension of some face centered cubic (FCC) metals (namely Au, Ag, Cu and Ni) at nano-level have been carried out. Sutton-Chen potential functions and velocity Verlet formulation of Noise-Hoover dynamic as well as periodic boundary conditions were applied. MD simulations at different loading rates and temperatures were conducted, and it was concluded that by increasing the temperature, maximum engineering stress decreases while engineering strain at failure is increasing. On the other hand, by increasing the loading rate both maximum engineering stress and strain at failure are increasing.

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